3&#39;-alkynyl abscisic acid derivatives as aba antagonists

ABSTRACT

The present application relates to novel 3′-unsaturated abscisic acid (ABA) derivatives of Formula (I) as ABA antagonists. For example, the present application relates to methods of using compounds of Formula (I) for reducing adverse effects of an ABA response in plants such as lentil and promoting germination. (I) The present application also relates to methods of using 3′-phenyl abscisic acid (ABA) derivatives of Formula (II) as ABA antagonists, for example, for reducing adverse effects of an ABA response in plants such as lentil and promoting germination. (II)

RELATED APPLICATIONS

The present application claims the benefit of priority from co-pendingU.S. Provisional Patent Application Ser. No. 62/769,331, filed on Nov.19, 2018, the contents of which are incorporated herein by reference intheir entirety.

FIELD

The present application relates to 3′-unsaturated abscisic acid (ABA)derivatives of Formula (I), to processes for their preparation and totheir use as ABA antagonists. In particular, the present applicationrelates to methods of using 3′-unsaturated ABA derivatives for reducingadverse affects of an ABA response in plants such as lentil andpromoting germination. Also included are methods of using3′-phenyl-substituted ABA derivatives of Formula for reducing adverseaffects of an ABA response in plants such as lentil and promotinggermination.

BACKGROUND

Pulse crop production in Saskatchewan has been rising steadily over thepast decades. In 2016, Saskatchewan's farmers seeded nearly 5.3 M acresof lentils, 2.2 M acres of field peas and 170,000 acres of chickpeas,and generated a total production of nearly 5.2 M metric tonnes. One ofthe main reasons for this increase is that growers have realizedsignificant financial benefits from pulse crops relative to cereal oroilseed options in their crop rotations. To maintain the sustainabilityof pulse production on the Prairies, problems such as poor germinationunder cold and wet conditions, non-uniform crop maturity especially fababean and chickpea, are an issue.

Seed dormancy and germination, to a large extend, is influenced by thelevels of the plant hormones gibberellic acid (GA) and abscisic acid(ABA). These hormones have been the subject of extensive research tounderstand their mechanism to improve germination and ultimately, cropestablishment and yield (Nonogaki et al 2014).¹ ABA involvement indormancy maintenance and germination inhibition has been demonstrated ina number of different ways, for example (1) with mutants impaired in ABAsignalling (e.g. viviparous corn); (2) through germination experimentsat low or high temperature where germination is delayed and ABA levelsare observed to increase; (3) in germination experiments in whichsupplied ABA delays germination in a concentration dependent manner; and(4) in transgenic plants in which ABA levels and signalling are altered.The range of temperatures suitable for seed germination varies with theplant species. In pulse crops, especially the warm season pulses such assoybean and dry bean, low temperature seriously limits germination andearly growth, and eventually results in yield loss. There are numerousreports that indicated germination under suboptimal temperatures canlead to increased ABA levels and slower germination in oilseeds andcereals and other species. Recent works have suggested that the use ofABA analogs may be able to overcome these problems. Differences in theplant physiological and molecular responses in response to changes inthe structure of the ABA analog molecules being applied have been welldocumented (Walker-Simmons et al. 1992, Wilen et al. 1993; Benson et al2015, Abrams and Loewen 2019).²⁻⁵ ABA-related seed dormancy, slowgermination and emergence of seedlings are all issues for plant breedersworking with wild relatives of cultivated species. These issues resultin long generation times that impede progress towards developingimproved varieties. ABA antagonist have potential to improve plantbreeding methods.

Annual economic losses due to plant pathogens are estimated to amount to10 to 16% of global crop production (Chakraborty and Newton 2011).⁶Numerous pathogens utilize plant hormone signaling systems to renderplants susceptible to diseases. ABA is normally thought of as a planthormone protecting plants from abiotic stress but recent research isuncovering diverse roles for ABA in plant pathogen interactions and thatABA can act directly or through other hormones such as jasmonate andsalicylate (Lievens et al. 2017; Forlani et al. 2019; Cao et al.2019).⁷⁻⁹ In wheat an ABC transporter LR34 for which ABA is a substrate,confers resistance to a number of fungal pathogens (Krattinger et al.2019).¹⁰ In contrast, Xanthomonas translucens acts in wheat byincreasing expression of the plant NCED that is the rate limiting enzymein ABA biosynthesis, leading to increased levels of ABA. Elevated ABAlevels enhance the spreading of a bacterial gene which down regulatesNPR1 rendering the plant susceptible to infection (Peng et al. 2019).¹¹In rice ABA suppresses salicylate-induced resistance to Rice Leaf BlightPathogen Xanthomonas oryzae (Xi et al. 2013).¹² On the pathogen side, itis known that several phytopathogenic fungi, including Botrytis cinereawhich causes grey mold diseases and Cercospera spp. that cause leafspots on a wide range of crop species, produce ABA as a virulence factorto promote disease development during infection (Takino et al. 2019;Mbengue et al. 2016).^(13,14)

Chickpea and faba bean are among the long season pulse crops. Chickpeain particular has a strong indeterminacy. The plants continue to growafter entering the regenerative stage so long as the environmentalconditions are conducive. Stress conditions (water, temperature ornitrogen) are needed to cease the growth of chickpea and turn the plantsto maturity. To date, desiccation treatment has been a common practiceto stop plant growth such as lentil, field pea, faba bean and chickpeaand prepare the crops for harvesting by removing moisture from plantsand late maturing areas of the field. The use of ABA antagonists isexpected to increase water loss by keeping the stomata open and in turnforce the crop to die down or to turn maturity.

Various ABA derivatives have been disclosed in the art. For example,Rajagopalan et al. 2016¹⁵ synthesized ABA antagonists using a processrequiring eleven separate steps, beginning from commercially availablestarting materials; Takeuchi et al. 2014¹⁶ synthesized a class of3′-sulfur ABA derivatives; and WO2016/007587¹⁷ provides a class of3′-substituted ABA derivatives. Song et al. 2019 reported a series of3′-alkyl substituted analogs with moderate antagonist properties inovercoming ABA-induced inhibition of germination.¹⁸

SUMMARY

The present application describes a novel class of 3′-unsaturated ABAderivatives that have been shown to reduce adverse effects of an ABAresponse in a plant, and that are relatively straightforward andinexpensive to prepare.

Accordingly, the present application includes a compound of Formula (I)or an enantiomer, salt, and/or solvate thereof:

wherein

L is —C═C— or —C≡C—;

R¹ is C₁₋₁₀alkyl, C₂₋₁₀alkenyl, C₂₋₁₀alkynyl, (CH₂)₀₋₂C₃₋₁₀cycloalkyl,(CH₂)₀₋₂aryl, (CH₂)₀₋₂heterocycloalkyl, or (CH₂)₀₋₂heteroaryl, eachbeing optionally substituted with one or more of halo, CN, OH, NH₂,C₁₋₁₀alkyl, C₂₋₁₀alkenyl, C₂₋₁₀alkynyl, NH(C₁₋₆alkyl),N(C₁₋₆alkyl)(C₁₋₆alkyl), OC₁₋₆alkyl, OC₂₋₆alkenyl, OC₂₋₆alkynyl,(CH₂)₀₋₂C₃₋₁₀cycloalkyl, (CH₂)₀₋₂aryl, (CH₂)₀₋₂heterocycloalkyl,(CH₂)₀₋₂heteroaryl, O(CH₂)₀₋₂C₃₋₁₀cycloalkyl, O(CH₂)₀₋₂aryl,O(CH₂)₀₋₂heterocycloalkyl, or O(CH₂)₀₋₂heteroaryl, the latter 16 groupsbeing optionally substituted with one or more of halo, OH, NH₂,C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl, OC₁₋₁₆alkyl, OC₂₋₆alkenyl, orOC₂₋₆alkynyl; andR² is H, C₁₋₁₀alkyl, C₂₋₁₀alkenyl, C₂₋₁₀alkynyl, cycloalkyl, aryl,heterocycloalkyl or heteroaryl, the latter 7 groups being optionallysubstituted with one or more of halo, OH, NH₂, C₁₋₆alkyl, C₂₋₆alkenyl,C₂₋₆alkynyl, OC₁₋₁₆alkyl, OC₂₋₆alkenyl, or OC₂₋₆alkynyl,wherein each alkyl, alkenyl, and alkynyl are optionallyfluorosubstituted.

In an embodiment, R¹ is (CH₂)₀₋₂aryl optionally substituted with one ormore of halo, CN, OH, NH₂, C₁₋₁₀alkyl, OC₁₋₆alkyl,(CH₂)₀₋₂C₃₋₁₀cycloalkyl, (CH₂)₀₋₂aryl, (CH₂)₀₋₂heterocycloalkyl,(CH₂)₀₋₂heteroaryl, O(CH₂)₀₋₂C₃₋₁₀cycloalkyl, O(CH₂)₀₋₂aryl,O(CH₂)₀₋₂heterocycloalkyl or O(CH₂)₀₋₂heteroaryl, the latter 10 groupsbeing optionally substituted with one or more of halo, OH, NH₂,C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl, OC₁₋₁₆alkyl, OC₂₋₆alkenyl, orOC₂₋₆alkynyl, wherein each alkyl, alkenyl, and alkynyl are optionallyfluorosubstituted.

In an embodiment, R¹ is C₁₋₁₀alkyl optionally substituted with one ormore of halo, CN, OH, NH₂, C₁₋₁₀alkyl, C₂₋₁₀alkenyl, C₂₋₁₀alkynyl,NH(C₁₋₆alkyl), N(C₁₋₆alkyl)(C₁₋₆alkyl), OC₁₋₆alkyl, OC₂₋₆alkenyl,OC₂₋₆alkynyl, (CH₂)₀₋₂C₃₋₁₀cycloalkyl, (CH₂)₀₋₂aryl,(CH₂)₀₋₂heterocycloalkyl, (CH₂)₀₋₂heteroaryl, O(CH₂)₀₋₂C₃₋₁₀cycloalkyl,O(CH₂)₀₋₂aryl, O(CH₂)₀₋₂heterocycloalkyl, or O(CH₂)₀₋₂heteroaryl, thelatter 16 groups being optionally substituted with one or more of halo,OH, NH₂, C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl, OC₁₋₁₆alkyl, OC₂₋₆alkenyl,or OC₂₋₆alkynyl, wherein each alkyl, alkenyl, and alkynyl are optionallyfluorosubstituted.

The application also includes a method for reducing adverse effects ofan ABA response comprising administering an effective amount of one ormore compounds of the application to a plant in need thereof.

The present application also includes a method for reducing adverseeffects of an ABA response in a plant in need thereof comprisingadministering an effective amount of one or more compounds of theFormula (II) or an enantiomer, salt, and/or solvate thereof, to theplant,

wherein:n is 0, 1, 2, or 3;each R³ is independently selected from OH, halo, C₁₋₁₀alkyl, OC₁₋₆alkyl,and O(CH₂)₀₋₂aryl, the latter 3 groups being optionally substituted withone or more of halo, OH, NH₂, C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl,OC₁₋₁₆alkyl, OC₂₋₆alkenyl, or OC₂₋₆alkynyl; andR⁴ is selected from H or C₁₋₁₀alkyl,wherein each alkyl, alkenyl, and alkynyl is optionallyfluorosubstituted.

Other features and advantages of the present application will becomeapparent from the following detailed description. It should beunderstood, however, that the detailed description and the specificexamples, while indicating embodiments of the application, are given byway of illustration only and the scope of the claims should not belimited by these embodiments, but should be given the broadestinterpretation consistent with the description as a whole

BRIEF DESCRIPTION OF DRAWINGS

The embodiments of the application will now be described in greaterdetail with reference to the attached drawings in which:

FIG. 1A is a bar graph showing the effect of exemplary compound 1019used alone or in combination with ABA on percent germination of lentilseed at a dosage of 10 μM ABA and 100 μM compound 1019 on day 1 comparedto ABA alone.

FIG. 1B is a bar graph showing the effect of exemplary compound 1019used alone or in combination with ABA on percent germination of lentilseed at a dosage of 10 μM ABA and 100 μM compound 1019 on day 2 comparedto ABA alone.

FIG. 2 shows lentil seeds on day two when treated with exemplarycompound 1019 used alone or in combination with ABA at a dosage of 10 μMABA and 100 μM compound 1019 on day 2 compared to ABA alone.

FIG. 3A shows the effect of exemplary compounds of the application andcomparative compounds on percent germination of lentil seed on day one.Exemplary compounds of the application at 10 uM promoted germination inthe presence of 10 uM ABA.

FIG. 3B shows the effect of exemplary compounds of the application andcomparative compounds on percent germination of lentil seed on day two.Exemplary compounds of the application overcame ABA-inhibition at 1:1ratio of compound to ABA.

FIG. 4 A to H show lentil seeds treated with exemplary compounds of theapplication and comparative compounds. (A) Control and 10 μM ABA; and(B-H) Lentils have been treated with from left: 1 μM Exemplary Compound,10 μM Exemplary Compound, 1 μM Exemplary Compound+10 μM ABA and 10 μMExemplary Compound+10 μM ABA. Exemplary compounds used were as follows:1019 (B), 1021 (C), 1022 (D), 1023 (E), 1024 (F), 1025 (G) andcomparative compound 1001 (H).

FIG. 5A and FIG. 5B are bar graphs showing lentil seed germinationassays with exemplary compound 1080 and exemplary compound 1090.

FIG. 6A, FIG. 6B and FIG. 6C are bar graphs showing lentil seedgermination assays with exemplary compounds 1091 and 1100.

FIG. 7A and FIG. 7B are graphs showing soybean germination assays withexemplary compound 1019. FIG. 7A is a bar graph showing the percentgermination at 48 h. FIG. 7B shows percent germination over time (24 h,48 h and 72 h post treatment).

FIG. 8 is a bar graph showing canary seed germination assays withexemplary compound 1019 and shows effects of ABA and/or exemplarycompound 1019.

FIG. 9A and FIG. 9B are bar graphs showing the results of Hard RedSpring wheat seedling growth studies with exemplary compound 1019. FIG.9A shows the total root growth at 72 h. FIG. 9B shows shoot root growthat 72 h post treatment.

FIG. 10 is a graph showing canola seed germination assay with exemplarycompound 1019 and shows effects of ABA and/or exemplary compound 1019 at2 days, 4 days, 6 days and 8 days post treatment.

FIG. 11A, FIG. 11B, FIG. 11C and FIG. 11D are bar graphs showing theimpact of ABA and exemplary compound 1019 on rice (FIG. 11A), barley(FIG. 11B), wheat (FIG. 11A), and Sorghum (FIG. 11D) radical elongation.FIG. 11A shows the effects of 5 uM ABA or 5 uM ABA+10 uM 1019 on radicallength of rice 4.5 days post treatment. Least Square mean: Ctrl:(A)=1.0666667; 1019: (A)=1.0363636; ABA+1019: (A)=0.8673913; H₂O:(A)=0.8568182; ABA: (B)=0.2727273. FIG. 11B shows the effects of 5 uMABA or 5 uM ABA+10 uM 1019 on radical length of barley 3.0 days posttreatment. Least Square mean: H₂O: (A)=3.1906250; Ctrl: (A)=3.1000000;ABA+1019: (A)=2.9300000; 1019: (A)=2.8300000; ABA: (B)=1.7181818. FIG.11C shows the effects of 5 uM ABA or 5 uM ABA+10 uM 1019 on radicallength of wheat 3.0 days post treatment. Least Square mean: ABA+1019:(A)=2.5386364; Ctrl: (A)=2.5069767; H₂O: (A)=2.4000000; 1019:(A)=2.3860465; ABA: (B)=1.7113636. FIG. 11D shows the effects of 10 uMABA or 10 uM ABA+20 uM 1019 on radical length of sorghum 3.0 days posttreatment. Least Square mean: H₂O: (A)=0.29090909; Ctrl:(AB)=0.26976744; ABA+1019: (B)=0.20454545; 1019: (B)=0.20444444; ABA:(C)=0.11707317. Results A, B and C are statistically different from eachother.

FIG. 12A is a bar graph showing the results of the lentil germinationassays with exemplary compound 1019 and GA, and showing the effect ofwater (first bar), 1% DMSO in water (second bar), 10 uM 1019 (third bar)and 10 uM 1019+100 uM GA (fourth bar) on lentil germination at day 1 today 7 post treatment.

FIG. 12B is a bar graph showing the results of the lentil emergenceassays with exemplary compound 1019 and GA, and showing the effect ofwater (first bar), 1% DMSO in water (second bar), 10 uM 1019 (third bar)and 10 uM 1019+100 uM GA (fourth bar) on lentil germination at day 3 today 9 post treatment.

FIG. 13 shows the effect of exemplary compound 1019 on ABA induciblegene expression.

FIG. 14 shows the antimicrobial activity of exemplary compound 1019.Arabidopsis plants were sprayed twice with Mock and a solution ofexemplary compound 1019 (100 μM), and leaves were detached forinoculation. Inoculated leaves were incubated under light for 24 hbefore photographs were taken.

DETAILED DESCRIPTION 1. Definitions

Unless otherwise indicated, the definitions and embodiments described inthis and other sections are intended to be applicable to all embodimentsand aspects of the present application herein described for which theyare suitable as would be understood by a person skilled in the art.

The term “compound of the application” or “compound of the presentapplication” and the like as used herein refers to a compound of Formula(I) or enantiomers, salts and/or solvates thereof.

The term “composition of the application” or “composition of the presentapplication” and the like as used herein refers to a compositioncomprising one or more compounds of the application and/or one or morecompounds of Formula (II) or enantiomers, salts and/or solvates thereof.

The term “and/or” as used herein means that the listed items arepresent, or used, individually or in combination. In effect, this termmeans that “at least one of” or “one or more” of the listed items isused or present. The term “and/or” with respect to salts and/or solvatesthereof means that the compounds of the application exist as individualsalts and hydrates, as well as a combination of, for example, a salt ofa solvate of a compound of the application.

As used in the present application, the singular forms “a”, “an” and“the” include plural references unless the content clearly dictatesotherwise. For example, an embodiment including “a negative response”should be understood to present certain aspects with one negative, ortwo or more additional negative responses.

In embodiments comprising an “additional” or “second” component oreffect, such as an additional or second adverse effect, the secondeffect as used herein is different from the other effects or firsteffect. A “third” adverse effect is different from the other, first, andsecond effects, and further enumerated or “additional” adverse effectsare similarly different.

As used in this application and claim(s), the words “comprising” (andany form of comprising, such as “comprise” and “comprises”), “having”(and any form of having, such as “have” and “has”), “including” (and anyform of including, such as “include” and “includes”) or “containing”(and any form of containing, such as “contain” and “contains”), areinclusive or open-ended and do not exclude additional, unrecitedelements or process steps.

The term “consisting” and its derivatives as used herein are intended tobe closed terms that specify the presence of the stated features,elements, components, groups, integers, and/or steps, and also excludethe presence of other unstated features, elements, components, groups,integers and/or steps.

The term “consisting essentially of”, as used herein, is intended tospecify the presence of the stated features, elements, components,groups, integers, and/or steps as well as those that do not materiallyaffect the basic and novel characteristic(s) of these features,elements, components, groups, integers, and/or steps.

The term “suitable” as used herein means that the selection of theparticular compound or conditions would depend on the specific syntheticmanipulation to be performed, the identity of the molecule(s) to betransformed and/or the specific use for the compound, but the selectionwould be well within the skill of a person trained in the art.

In embodiments of the present application, the compounds describedherein may have at least one asymmetric center. Where compounds possessmore than one asymmetric center, they may exist as diastereomers. It isto be understood that all such isomers and mixtures thereof in anyproportion are encompassed within the scope of the present application.It is to be further understood that while the stereochemistry of thecompounds may be as shown in any given compound listed herein, suchcompounds may also contain certain amounts (for example, less than 20%,suitably less than 10%, more suitably less than 5%) of compounds of thepresent application having an alternate stereochemistry. It is intendedthat any optical isomers, as separated, pure or partially purifiedoptical isomers or racemic mixtures thereof are included within thescope of the present application.

The compounds of the present application may also exist in differenttautomeric forms and it is intended that any tautomeric forms which thecompounds form, as well as mixtures thereof, are included within thescope of the present application.

The compounds of the present application may further exist in varyingpolymorphic forms and it is contemplated that any polymorphs, ormixtures thereof, which form are included within the scope of thepresent application.

The present description refers to a number of chemical terms andabbreviations used by those skilled in the art. Nevertheless,definitions of selected terms are provided for clarity and consistency.

The terms “about”, “substantially” and “approximately” as used hereinmean a reasonable amount of deviation of the modified term such that theend result is not significantly changed. These terms of degree should beconstrued as including a deviation of at least ±5% of the modified termif this deviation would not negate the meaning of the word it modifiesor unless the context suggests otherwise to a person skilled in the art.

The term “alkyl” as used herein, whether it is used alone or as part ofanother group, means straight or branched chain, saturated alkyl groups.The number of carbon atoms that are possible in the referenced alkylgroup are indicated by the prefix “C_(n1-n2)”. For example, the termC₁₋₁₀alkyl means an alkyl group having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10carbon atoms.

The term “alkylene”, whether it is used alone or as part of anothergroup, means straight or branched chain, saturated alkylene group, thatis, a saturated carbon chain that contains substituents on two of itsends. The number of carbon atoms that are possible in the referencedalkylene group are indicated by the prefix “C_(n1-n2)”. For example, theterm C₂₋₆alkylene means an alkylene group having 2, 3, 4, 5 or 6 carbonatoms.

The term “alkenyl” as used herein, whether it is used alone or as partof another group, means straight or branched chain, unsaturated alkylgroups containing at least one double bond. The number of carbon atomsthat are possible in the referenced alkylene group are indicated by theprefix “C_(n1-n2)”. For example, the term C₂₋₆alkenyl means an alkenylgroup having 2, 3, 4, 5 or 6 carbon atoms and at least one double bond.

The term “alkynyl” as used herein, whether it is used alone or as partof another group, means straight or branched chain, unsaturated alkynylgroups containing at least one triple bond. The number of carbon atomsthat are possible in the referenced alkyl group are indicated by theprefix “C_(n1-n2)”. For example, the term C₂₋₆alkynyl means an alkynylgroup having 2, 3, 4, 5 or 6 carbon atoms.

The term “cycloalkyl,” as used herein, whether it is used alone or aspart of another group, means a saturated carbocyclic group containing anumber of carbon atoms and one or more rings. The number of carbon atomsthat are possible in the referenced cycloalkyl group are indicated bythe numerical prefix “C_(n1-n2)”. For example, the term C₃₋₁₀cycloalkylmeans a cycloalkyl group having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms.When a cycloalkyl group contains more than one ring, the rings may befused, bridged, spirofused or linked by a bond.

The term “aryl” as used herein, whether it is used alone or as part ofanother group, refers to carbocyclic groups containing at least onearomatic ring and contains either 6, 9 or 10 carbon atoms, such asphenyl, indanyl or naphthyl.

The term “heterocycloalkyl” as used herein, whether it is used alone oras part of another group, refers to cyclic groups containing at leastone non-aromatic ring containing from 3 to 10 atoms in which one or moreof the atoms are a heteroatom selected from O, S and N and the remainingatoms are C. Heterocycloalkyl groups are either saturated or unsaturated(i.e. contain one or more double bonds). When a heterocycloalkyl groupcontains the prefix C_(n1-n2) this prefix indicates the number of carbonatoms in the corresponding carbocyclic group, in which one or more,suitably 1 to 5, of the ring atoms is replaced with a heteroatom asdefined above.

The term “heteroaryl” as used herein, whether it is used alone or aspart of another group, refers to cyclic groups containing at least oneheteroaromatic ring containing 5, 6, 8, 9 or 10 atoms in which one ormore of the atoms are a heteroatom selected from O, S and N and theremaining atoms are C. When a heteroaryl group contains the prefixC_(n1-n2) this prefix indicates the number of carbon atoms in thecorresponding carbocyclic group, in which one or more, suitably 1 to 5,of the ring atoms is replaced with a heteroatom as defined above.

All cyclic groups, including aryl and cyclo groups, contain one or morethan one ring (i.e. are polycyclic). When a cyclic group contains morethan one ring, the rings may be fused, bridged, spirofused or linked bya bond.

The term “fluorosubstituted” refers to the substitution of one or more,including all, available hydrogens in a referenced group with fluorine.

The term “available”, as in “available hydrogen atoms” or “availableatoms” refers to atoms that would be known to a person skilled in theart to be capable of replacement by a substituent.

The term “salt” means an acid addition salt or a basic addition salt.The term “salts” embraces salts commonly used to form addition salts offree acids or free bases and those compatible with the treatment ofplants.

The term “solvate” as used herein means a compound, or a salt or prodrugof a compound, wherein molecules of a suitable solvent are incorporatedin the crystal lattice. A suitable solvent is physiologically tolerableat the dosage administered

The term “protecting group” or “PG” and the like as used herein refersto a chemical moiety which protects or masks a reactive portion of amolecule to prevent side reactions in those reactive portions of themolecule, while manipulating or reacting a different portion of themolecule. After the manipulation or reaction is complete, the protectinggroup is removed under conditions that do not degrade or decompose theremaining portions of the molecule. The selection of a suitableprotecting group can be made by a person skilled in the art. Manyconventional protecting groups are known in the art, for example asdescribed in “Protective Groups in Organic Chemistry” McOmie, J. F. W.Ed., Plenum Press, 1973, in Greene, T. W. and Wuts, P. G. M.,“Protective Groups in Organic Synthesis”, John Wiley & Sons, 3^(rd)Edition, 1999 and in Kocienski, P. Protecting Groups, 3rd Edition, 2003,Georg Thieme Verlag (The Americas).

The term “abscisic acid” (ABA) refers to a compound having the IUPACname:(2Z,4E)-5-[(1S)-1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl]-3-methylpenta-2,4-dienoicacid and having the chemical formula:

The term “1001” refers to a compound having the IUPAC name:(2Z,4E)-5-((S)-(1-hydroxy-6-(3-hydroxypropoxy)-2,2-dimethyl-4-oxo-1,2,3,4-tetrahydronaphthalen-1-yl)-3-methylpenta-2,4-dienoicacid and having the chemical formula:

The term “1002” refers to a compound having the IUPAC name:(2Z,4E)-5-(S)-(3-(hexylthio)-1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl)-3-methylpenta-2,4-dienoicacid and having the chemical formula:

As used herein, the term “effective amount” means an amount effective,at dosages and for periods of time, necessary to achieve a desiredresult.

The term “desired result” as used herein is any positive effect on plantgrown and development.

When used, for example, with respect to the methods of treatment, uses,and compositions of the application, a plant, for example a plant “inneed thereof” is a cell, seed, part of a plant or plant in which ABAplays a role in plant growth and development

The term “administered” as used herein means administration of atherapeutically effective amount of one or more compounds orcompositions of the application and/or one or more compounds of Formula(II) or enantiomers, salts and/or solvates thereof, to a cell, seed orto a plant.

The term “ABA antagonist” as used herein means a compound that inhibitsa negative response to ABA signaling in a plant.

The term “ABA response” as used herein means a response that has anegative or undesirable impact on plant growth and development as aresult of the presence of ABA in the plant, including endogenouslyproduced ABA or ABA from an external source.

The term “reduce” or “reducing” as used herein with respect to theadverse affects of an ABA response refers to any decrease in adverseaffects of an ABA response compared a control, such as otherwiseidentical conditions except in the absence of one or more compounds ofthe application and/or one or more compounds of Formula II, orenantiomers, salts and/or solvates thereof.

The term “ABA producing plant pathogen” as used herein means a plantpathogen that elicits an ABA response in a plant, including by inducingABA production by the plant and providing an external source of ABA.

The term “ABA producing plant pathogen infection” or refers to aninvasion of plant cells by a foreign undesirable ABA producing plantpathogen.

The terms “to treat”, “treating” and “treatment” as used herein and asis well understood in the art, means an approach for obtainingbeneficial or desired results, including clinical results. Beneficial ordesired clinical results include, but are not limited to, diminishmentof extent of infection, stabilization (i.e. not worsening) of the stateof the ABA producing plant pathogen infection, preventing spread of theABA producing plant pathogen infection, delay or slowing of infectionprogression, amelioration or palliation of the ABA producing plantpathogen infectious state, diminishment of the reoccurrence of ABAproducing plant pathogen infection, diminishment, stabilization,alleviation or amelioration of one or more diseases, disorders orconditions arising from the ABA producing plant pathogen infection,diminishment of the reoccurrence of one or more diseases, disorders orconditions arising from the ABA producing plant pathogen infection, andremission of the ABA producing plant pathogen infection and/or one ormore symptoms or conditions arising from the ABA producing plantpathogen infection, whether partial or total, whether detectable orundetectable. “To treat”, “treating” and “treatment” can also meanprolonging survival as compared to expected survival if not receivingtreatment. “To treat”, “treating” and “treatment” as used herein alsoinclude prophylactic treatment. For example, a plant with an early ABAproducing plant pathogen infection is treated to prevent progression, oralternatively a plant in remission is treated to prevent recurrence.

“Palliating” an infection, disease, disorder and/or condition means thatthe extent and/or undesirable manifestations of an infection, disease,disorder and/or condition are lessened and/or time course of theprogression is slowed or lengthened, as compared to not treating theinfection, disease, disorder and/or condition.

The term “prevention” or “prophylaxis” and the like as used hereinrefers to a reduction in the risk or probability of a plant becomingafflicted with a ABA producing plant pathogen infection and/or adisease, disorder and/or condition arising from a ABA producing plantpathogen infection or manifesting a symptom associated with a ABAproducing plant pathogen infection and/or a disease, disorder and/orcondition arising from a ABA producing plant pathogen infection.

The term “composition” as used herein refers to a composition of matterfor plant-based use.

The term “plant” as used herein refers to any species or genera of plantin which ABA signaling plays a role in regulating plant development.

II. Compounds and Compositions of the Application

The present application describes a novel class of 3′-unsaturated ABAderivatives that can regulate plant growth, and that are relativelystraightforward and inexpensive to prepare.

Accordingly, the present application includes a compound of Formula (I)or an enantiomer, salt, and/or solvate thereof:

wherein

L is —C═C— or —C≡C—;

R¹ is C₁₋₁₀alkyl, C₂₋₁₀alkenyl, C₂₋₁₀alkynyl, (CH₂)₀₋₂C₃₋₁₀cycloalkyl,(CH₂)₀₋₂aryl, (CH₂)₀₋₂heterocycloalkyl, or (CH₂)₀₋₂heteroaryl, eachbeing optionally substituted with one or more of halo, CN, OH, NH₂,C₁₋₁₀alkyl, C₂₋₁₀alkenyl, C₂₋₁₀alkynyl, NH(C₁₋₆alkyl),N(C₁₋₆alkyl)(C₁₋₆alkyl), OC₁₋₆alkyl, OC₂₋₆alkenyl, OC₂₋₆alkynyl,(CH₂)₀₋₂C₃₋₁₀cycloalkyl, (CH₂)₀₋₂aryl, (CH₂)₀₋₂heterocycloalkyl,(CH₂)₀₋₂heteroaryl, O(CH₂)₀₋₂C₃₋₁₀cycloalkyl, O(CH₂)₀₋₂aryl,O(CH₂)₀₋₂heterocycloalkyl, or O(CH₂)₀₋₂heteroaryl, the latter 16 groupsbeing optionally substituted with one or more of halo, OH, NH₂,C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl, OC₁₋₁₆alkyl, OC₂₋₆alkenyl, orOC₂₋₆alkynyl; andR² is H, C₁₋₁₀alkyl, C₂₋₁₀alkenyl, C₂₋₁₀alkynyl, cycloalkyl, aryl,heterocycloalkyl or heteroaryl, the latter 7 groups being optionallysubstituted with one or more of halo, OH, NH₂, C₁₋₆alkyl, C₂₋₆alkenyl,C₂₋₆alkynyl, OC₁₋₁₆alkyl, OC₂₋₆alkenyl, or OC₂₋₆alkynyl,wherein each alkyl, alkenyl, and alkynyl are optionallyfluorosubstituted.

The present application also includes a compound of Formula (I) or anenantiomer, salt, and/or solvate thereof:

whereinR¹ is C₁₋₁₀alkyl, C₂₋₁₀alkenyl, C₂₋₁₀alkynyl, (CH₂)₀₋₂C₃₋₁₀cycloalkyl,(CH₂)₀₋₂aryl, (CH₂)₀₋₂heterocycloalkyl, or (CH₂)₀₋₂heteroaryl, eachbeing optionally substituted with one or more of halo, CN, OH, NH₂,C₁₋₁₀alkyl, C₂₋₁₀alkenyl, C₂₋₁₀alkynyl, NH(C₁₋₆alkyl),N(C₁₋₆alkyl)(C₁₋₆alkyl), OC₁₋₆alkyl, OC₂₋₆alkenyl, OC₂₋₆alkynyl,(CH₂)₀₋₂C₃₋₁₀cycloalkyl, (CH₂)₀₋₂aryl, (CH₂)₀₋₂heterocycloalkyl,(CH₂)₀₋₂heteroaryl, O(CH₂)₀₋₂C₃₋₁₀cycloalkyl, O(CH₂)₀₋₂aryl,O(CH₂)₀₋₂heterocycloalkyl, or O(CH₂)₀₋₂heteroaryl, the latter 16 groupsbeing optionally substituted with one or more of halo, OH, NH₂,C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl, OC₁₋₁₆alkyl, OC₂₋₆alkenyl, orOC₂₋₆alkynyl; andR² is H, C₁₋₁₀alkyl, C₂₋₁₀alkenyl, C₂₋₁₀alkynyl, cycloalkyl, aryl,heterocycloalkyl or heteroaryl, the latter 7 groups being optionallysubstituted with one or more of halo, OH, NH₂, C₁₋₆alkyl, C₂₋₆alkenyl,C₂₋₆alkynyl, OC₁₋₁₆alkyl, OC₂₋₆alkenyl, or OC₂-6alkynyl,wherein each alkyl, alkenyl, and alkynyl are optionallyfluorosubstituted.

In an embodiment, R¹ is (CH₂)₀₋₂aryl optionally substituted with one ormore of halo, CN, OH, NH₂, C₁₋₁₀alkyl, C₂₋₁₀alkenyl, C₂₋₁₀alkynyl,NH(C₁₋₆alkyl), N(C₁₋₆alkyl)(C₁₋₆alkyl), OC₁₋₆alkyl, OC₂₋₆alkenyl,OC₂₋₆alkynyl, (CH₂)₀₋₂C₃₋₁₀cycloalkyl, (CH₂)₀₋₂aryl,(CH₂)₀₋₂heterocycloalkyl, (CH₂)₀₋₂heteroaryl, O(CH₂)₀₋₂C₃₋₁₀cycloalkyl,O(CH₂)₀₋₂aryl, O(CH₂)₀₋₂heterocycloalkyl or O(CH₂)₀₋₂heteroaryl, thelatter 16 groups being optionally substituted with one or more of halo,OH, NH₂, C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl, OC₁₋₁₆alkyl, OC₂₋₆alkenyl,or OC₂₋₆alkynyl, wherein each alkyl, alkenyl, and alkynyl are optionallyfluorosubstituted.

In an embodiment, R¹ is (CH₂)₀₋₂aryl optionally substituted with one ormore of halo, CN, OH, NH₂, C₁₋₁₀alkyl, OC₁₋₆alkyl,(CH₂)₀₋₂C₃₋₁₀cycloalkyl, (CH₂)₀₋₂aryl, (CH₂)₀₋₂heterocycloalkyl,(CH₂)₀₋₂heteroaryl, O(CH₂)₀₋₂C₃₋₁₀cycloalkyl, O(CH₂)₀₋₂aryl,O(CH₂)₀₋₂heterocycloalkyl or O(CH₂)₀₋₂heteroaryl, the latter 10 groupsbeing optionally substituted with one or more of halo, OH, NH₂,C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl, OC₁₋₁₆alkyl, OC₂₋₆alkenyl, orOC₂₋₆alkynyl, wherein each alkyl, alkenyl, and alkynyl are optionallyfluorosubstituted.

In an embodiment, R¹ is aryl optionally substituted with one or more ofOH, halo, C₁₋₁₀alkyl, OC₁₋₆alkyl, or O(CH₂)₀₋₂aryl, wherein each alkyl,alkenyl, and alkynyl are optionally fluorosubstituted.

In an embodiment, R¹ is aryl optionally substituted with one or more ofhalo, C₁₋₁₀alkyl, OC₁₋₆alkyl, or O(CH₂)₀₋₂aryl, wherein each alkyl,alkenyl, and alkynyl are optionally fluorosubstituted.

In an embodiment, R¹ is aryl. In an embodiment, R¹ is aryl substitutedwith one or more OH. In an embodiment, R¹ is aryl substituted withO(CH₂)₀₋₂aryl. In an embodiment, R¹ is aryl substituted with one or morehalo. In an embodiment, R¹ is aryl substituted with one or more fluoro.

In an embodiment, R¹ is aryl substituted with C₁₋₁₀alkyl, wherein alkylis optionally fluorosubstituted. In an embodiment, R¹ is arylsubstituted with one or more of methyl, ethyl or CF₃.

In an embodiment, R¹ is aryl substituted with OC₁₋₆alkyl, wherein alkylis optionally fluorosubstituted. In an embodiment, R¹ is arylsubstituted with one or more of OCH₃ or OCF₃.

In an embodiment, R¹ is C₁₋₁₀alkyl optionally substituted with one ormore of halo, CN, OH, NH₂, C₁₋₁₀alkyl, C₂₋₁₀alkenyl, C₂₋₁₀alkynyl,NH(C₁₋₆alkyl), N(C₁₋₆alkyl)(C₁₋₆alkyl), OC₁₋₆alkyl, OC₂₋₆alkenyl,OC₂₋₆alkynyl, (CH₂)₀₋₂C₃₋₁₀cycloalkyl, (CH₂)₀₋₂aryl,(CH₂)₀₋₂heterocycloalkyl, (CH₂)₀₋₂heteroaryl, O(CH₂)₀₋₂C₃₋₁₀cycloalkyl,O(CH₂)₀₋₂aryl, O(CH₂)₀₋₂heterocycloalkyl, or O(CH₂)₀₋₂heteroaryl, thelatter 16 groups being optionally substituted with one or more of halo,OH, NH₂, C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl, OC₁₋₁₆alkyl, OC₂₋₆alkenyl,or OC₂₋₆alkynyl, wherein each alkyl, alkenyl, and alkynyl are optionallyfluorosubstituted.

In an embodiment, R¹ is C₁₋₁₀alkyl optionally substituted with one ormore of halo, CN, OH, NH₂, C₁₋₁₀alkyl, C₂₋₁₀alkenyl, or C₂₋₁₀alkynyl,wherein each alkyl, alkenyl, and alkynyl are optionallyfluorosubstituted.

In an embodiment, R¹ is C₁₋₁₀alkyl substituted with one or more of OHand C₁₋₁₀alkyl, wherein alkyl is optionally fluorosubstituted.

In an embodiment, R¹ is C₂₋₁₀alkenyl optionally substituted with one ormore of halo, CN, OH, NH₂, C₁₋₁₀alkyl, C₂₋₁₀alkenyl, C₂₋₁₀alkynyl,NH(C₁₋₆alkyl), N(C₁₋₆alkyl)(C₁₋₆alkyl), OC₁₋₆alkyl, OC₂₋₆alkenyl,OC₂₋₆alkynyl, (CH₂)₀₋₂C₃₋₁₀cycloalkyl, (CH₂)₀₋₂aryl,(CH₂)₀₋₂heterocycloalkyl, (CH₂)₀₋₂heteroaryl, O(CH₂)₀₋₂C₃₋₁₀cycloalkyl,O(CH₂)₀₋₂aryl, O(CH₂)₀₋₂heterocycloalkyl, or O(CH₂)₀₋₂heteroaryl, thelatter 16 groups being optionally substituted with one or more of halo,OH, NH₂, C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl, OC₁₋₁₆alkyl, OC₂₋₆alkenyl,or OC₂₋₆alkynyl, wherein each alkyl, alkenyl, and alkynyl are optionallyfluorosubstituted.

In an embodiment, R¹ is C₂₋₁₀alkenyl optionally substituted with one ormore of halo, CN, OH, NH₂, C₁₋₁₀alkyl, C₂₋₁₀alkenyl, or C₂₋₁₀alkynyl,wherein each alkyl, alkenyl, and alkynyl are optionallyfluorosubstituted.

In an embodiment, R¹ is C₂₋₆alkenyl substituted with one or more of OHand C₁₋₁₀alkyl, wherein alkyl is optionally fluorosubstituted. In anembodiment, R¹ is (CH₂)₀₋₂C₃₋₁₀cycloalkyl optionally substituted withone or more of halo, CN, OH, NH₂, C₁₋₁₀alkyl, C₂₋₁₀alkenyl,C₂₋₁₀alkynyl, NH(C₁₋₆alkyl), N(C₁₋₆alkyl)(C₁₋₆alkyl), OC₁₋₆alkyl,OC₂₋₆alkenyl, OC₂₋₆alkynyl, (CH₂)₀₋₂C₃₋₁₀cycloalkyl, (CH₂)₀₋₂aryl,(CH₂)₀₋₂heterocycloalkyl, (CH₂)₀₋₂heteroaryl, O(CH₂)₀₋₂C₃₋₁₀cycloalkyl,O(CH₂)₀₋₂aryl, O(CH₂)₀₋₂heterocycloalkyl, or O(CH₂)₀₋₂heteroaryl, thelatter 16 groups being optionally substituted with one or more of halo,OH, NH₂, C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl, OC₁₋₁₆alkyl, OC₂₋₆alkenyl,or OC₂₋₆alkynyl, wherein each alkyl, alkenyl, and alkynyl are optionallyfluorosubstituted.

In an embodiment, R¹ is C₃₋₁₀cycloalkyl In an embodiment, R¹ isC₃₋₁₀cycloalkyl optionally substituted with one or more of halo, CN, OH,NH₂, C₁₋₁₀alkyl, C₂₋₁₀alkenyl, or C₂₋₁₀alkynyl, wherein each alkyl,alkenyl, and alkynyl are optionally fluorosubstituted.

In an embodiment, R² is H or C₁₋₁₀alkyl. In an embodiment, R² is H orCH₃.

In an embodiment, L is —C═C—. In an embodiment, L is —C═C—.

In an embodiment, the compounds of Formula (I) have the followingstereochemistry:

In an embodiment, the compounds of Formula (I) wherein L is —C═C havethe following stereochemistry:

In an embodiment, the compound of Formula (I) is selected from thecompounds listed below:

Compound Example I.D # Structures 1018 1

1019 2

1021 3

1022 4

1023 5

1024 6

1025 7

1059 8

1063 9

1090 10 

1091 11 

1100 12 

or a salt, and/or solvate thereof.

In an embodiment the salt is an acid addition salt or a base additionsalt.

The selection of a suitable salt may be made by a person skilled in theart (see, for example, S. M. Berge, et al., “Pharmaceutical Salts,” J.Pharm. Sci. 1977, 66, 1-19).

An acid addition salt suitable for, or compatible with, the treatment ofsubjects is any non-toxic organic or inorganic acid addition salt of anybasic compound. Basic compounds that form an acid addition salt include,for example, compounds comprising an amine group. Illustrative inorganicacids which form suitable salts include hydrochloric, hydrobromic,sulfuric, nitric and phosphoric acids, as well as acidic metal saltssuch as sodium monohydrogen orthophosphate and potassium hydrogensulfate. Illustrative organic acids which form suitable salts includemono-, di- and tricarboxylic acids. Illustrative of such organic acidsare, for example, acetic, trifluoroacetic, propionic, glycolic, lactic,pyruvic, malonic, succinic, glutaric, fumaric, malic, tartaric, citric,ascorbic, maleic, hydroxymaleic, benzoic, hydroxybenzoic, phenylacetic,cinnamic, mandelic, salicylic, 2-phenoxybenzoic, p-toluenesulfonic acidand other sulfonic acids such as methanesulfonic acid, ethanesulfonicacid and 2-hydroxyethanesulfonic acid. In an embodiment, the mono- ordi-acid salts are formed, and such salts exist in either a hydrated,solvated or substantially anhydrous form. In general, acid additionsalts are more soluble in water and various hydrophilic organicsolvents, and generally demonstrate higher melting points in comparisonto their free base forms. The selection criteria for the appropriatesalt will be known to one skilled in the art. Other non-pharmaceuticallyacceptable salts such as but not limited to oxalates may be used, forexample in the isolation of compounds of the application for laboratoryuse, or for subsequent conversion to a pharmaceutically acceptable acidaddition salt.

A base addition salt suitable for, or compatible with, the treatment ofsubjects is any non-toxic organic or inorganic base addition salt of anyacidic compound. Acidic compounds that form a basic addition saltinclude, for example, compounds comprising a carboxylic acid group.Illustrative inorganic bases which form suitable salts include lithium,sodium, potassium, calcium, magnesium or barium hydroxide as well asammonia. Illustrative organic bases which form suitable salts includealiphatic, alicyclic or aromatic organic amines such as isopropylamine,methylamine, trimethylamine, picoline, diethylamine, triethylamine,tripropylamine, ethanolamine, 2-dimethylaminoethanol,2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine,caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine,glucosamine, methylglucamine, theobromine, purines, piperazine,piperidine, N-ethylpiperidine, polyamine resins, and the like. Exemplaryorganic bases are isopropylamine, diethylamine, ethanolamine,trimethylamine, dicyclohexylamine, choline, and caffeine. The selectionof the appropriate salt may be useful, for example, so that an esterfunctionality, if any, elsewhere in a compound is not hydrolyzed. Theselection criteria for the appropriate salt will be known to one skilledin the art.

In an embodiment the salt is a base addition salt.

Solvates of compounds of the application include, for example, thosemade with solvents that are pharmaceutically acceptable. Examples ofsuch solvents include water (resulting solvate is called a hydrate) andethanol and the like.

The compounds of the present application are suitably formulated in aconventional manner into compositions using one or more carriers.Accordingly, the present application also includes a compositioncomprising one or more compounds of the application and a carrier. In anembodiment, the carrier is any carrier compatible or suitable foragricultural use, such as water.

A compound of the application including salts and/or solvates thereof issuitably used on their own but will generally be administered in theform of a composition in which the one or more compounds of theapplication (the active ingredient) is in association with an acceptablecarrier. Depending on the mode of administration, the composition willcomprise from about 0.05 wt % to about 99 wt % or about 0.10 wt % toabout 70 wt %, of the active ingredient, and from about 1 wt % to about99.95 wt % or about 30 wt % to about 99.90 wt % of an acceptablecarrier, all percentages by weight being based on the total composition.

A compound of the application is either used alone or in combinationwith other known agents useful for regulating plant development. Whenused in combination with other agents useful for regulating plantdevelopment, it is an embodiment that a compound of the application isadministered contemporaneously with those agents. As used herein,“contemporaneous administration” of two substances to a subject meansproviding each of the two substances so that they are both active in thesubject at the same time.

In an embodiment, the other agent is a plant growth regulator.

In an embodiment, the other agent is an agricultural product.

In the above, the term “a compound” also includes embodiments whereinone or more compounds are referenced.

III. Methods and Uses of the Application

The compounds of the application have been shown to reduce adverseeffects of an ABA response in a plant. In particular, it hassurprisingly been shown that the compounds of the application can reduceadverse effects of an ABA response in seeds such as lentil seeds,soybean seeds, canary seed, wheat seed, canola seed, rice seed, barleyseed, and sorghum seed and promote germination. It has further beensurprisingly shown that the compounds of the application can reduceadverse effects of an ABA response arising from an ABA producing plantpathogen infection, such as an infection from Botrytis cinerea. In anembodiment, the compounds of the application act as ABA antagonists.

Accordingly, the present application includes a method for reducingadverse effects of an ABA response in a plant in need thereof comprisingadministering an effective amount of one or more compounds of theapplication to the plant. The application also includes a use of one ormore compounds of the application for reducing adverse effects of an ABAresponse in a plant. The application further includes one or morecompounds of the application for use to reduce adverse effects of an ABAresponse in a plant.

In an embodiment, the plant is a canola, soybean, canary, sorghum,lentil, chickpea, Arabidopsis, faba bean, soybean, corn, rice, wheat,rye, barley, or fruit plant.

In an embodiment, the plant is a canola, lentil, chickpea, Arabidopsis,faba bean, soybean, corn, rice, wheat, rye, barley, or fruit plant.

In an embodiment, the plant is a lentil, soybean, canary, wheat, canola,rice, barley, or sorghum plant.

In an embodiment, the fruit plant is table or wine grapes.

In an embodiment, the fruit plant is a stone fruit plant. In anembodiment, the stone fruit plant is apricot, cherry, peach or plum.

In an embodiment, the fruit plant is strawberry, blueberry, raspberry,or blackberry.

In an embodiment, the fruit plant is pome fruit. In an embodiment, thepome fruit is apple, pear, or cherry.

In an embodiment, fruit plant is eggplant, pepper, or tomato.

In an embodiment, the fruit plant is cucurbit. In an embodiment, thecurcubit is cucumber, pumpkin, muskmelon, squash, or zucchini.

In an embodiment, the fruit plant is a tree nut plant. In an embodiment,the tree nut plant is walnut, chestnut, or hickory.

In an embodiment, the plant is leafy vegetable, or pasture and turfgrass.

In an embodiment, the plant is oat, flax, mustard, ornamental, or sugarcane.

In an embodiment, the methods and uses of the application comprisecontacting the seed of the plant with an effective amount of thecompound of the application or salt and/or solvate thereof.

In an embodiment, a reduction in adverse affects of an ABA responseincludes, but is not limited to, delayed or inhibited seed germinationand/or plant dessication, over-ripening of fruit, slow bud breakingand/or slow plant growth, for example, reduced or inhibited seedlinggrowth, delayed or inhibited plant emergence, and/or reduced orinhibited plant flowering In an embodiment, the reduction in adverseaffects of an ABA response occur under stress conditions, such as coldhear or high salt. In an embodiment, the compounds of the applicationpromote germination of seeds under stress conditions, overcomingseed-produced ABA that slows germination. In an embodiment, thecompounds delay over ripening of fruit and hasten bud break inhibited bycool conditions, and/or promote growth of plants under stressconditions.

In the context of reducing adverse affects of an ABA response, aneffective amount of the compound of the application or a salt and/orsolvate thereof, is an amount that, for example, reduces the adverseaffects compared to the negative response without administration of thecompound of the application, or a salt and/or solvate thereof.

In an embodiment, the ABA response arises from an ABA producing plantpathogen infection.

In an embodiment, the ABA producing plant pathogen is a fungus,bacterium, protist, nematode or virus. In an embodiment, the ABAproducing plant pathogen is a fungus. In an embodiment, the fungus isBotrytis cinerea or Cercospera spp. In an embodiment, the fungus isBotrytis cinerea.

In an embodiment, the ABA producing plant pathogen is a bacterium. In anembodiment, the bacterium is Xanthomonas oryzae pv oryzae or Xanthomonastranslucens.

It would be appreciated by the skilled person that Xanthomonas oryzae pvoryzae promotes leaf blight, for example, in rice (Xu et al 2013)²², andXanthomonas translucens promotes leaf streak, for example in wheat (Penget al 2019)¹¹.

In an embodiment, the effective amount of the compound of theapplication or a salt and/or solvate thereof to be administered to theplant is about 0.1 μM to about 600 μM, about 1 μM to about 500 μM, orabout 5 μM to about 250 μM.

It has been shown that compounds of the application can reduce adverseeffects of an ABA response arising from an infection of an ABA producingplant pathogen such as Botrytis cinerea. Accordingly, the presentapplication also includes a method for treating or preventing an ABAproducing plant pathogen infection in a plant in need thereof comprisingadministering an effective amount of one or more compounds of theapplication to the plant.

The application also includes a use of one or more compounds of theapplication for treating or preventing an ABA producing plant pathogeninfection in a plant. The application further includes one or morecompounds of the application for use for treating or preventing an ABAproducing plant pathogen infection in a plant.

The present application also includes a method for treating orpreventing a disease, disorder or condition in a plant arising from anABA producing plant pathogen infection comprising administering aneffective amount of one or more compounds of the application to a plantin need thereof.

The application also includes a use of one or more compounds of theapplication for treating or preventing a disease, disorder or conditionarising from an ABA producing plant pathogen infection in a plant. Theapplication further includes one or more compounds of the applicationfor use for treating or preventing a disease, disorder or conditionarising from an ABA producing plant pathogen infection in a plant.

It has further been surprisingly shown that compounds of Formula (II)can also reduce adverse effects of an ABA response, for example, inseeds such as lentil seeds. Therefore, in an embodiment, the compoundsof Formula (II) also act as ABA antagonists.

Accordingly, the present application also includes a method for reducingadverse effects of an ABA response in a plant in need thereof comprisingadministering an effective amount of one or more compounds of theFormula (II) or an enantiomer, salt, and/or solvate thereof, to theplant,

wherein:n is 0, 1, 2, or 3;R³ is selected from OH, halo, C₁₋₁₀alkyl, OC₁₋₆alkyl, and O(CH₂)₀₋₂aryl,the latter 3 groups being optionally substituted with one or more ofhalo, OH, NH₂, C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl, OC₁₋₁₆alkyl,OC₂₋₆alkenyl, or OC₂₋₆alkynyl; andR⁴ is selected from H or C₁₋₁₀alkyl,wherein each alkyl, alkenyl, and alkynyl is optionallyfluorosubstituted.

The application also includes a use of one or more compounds of Formula(II) for reducing adverse effects of an ABA response in a plant. Theapplication further includes one or more compounds of Formula (II) foruse to reduce adverse effects of an ABA response in a plant.

In an embodiment is 0, 1 or 2. In an embodiment n is 0 or 1. In anembodiment n is 0.

In an embodiment, R³ is not present (i.e. n is 0). In an embodiment, R³is selected from OH, halo, C₁₋₁₀alkyl, and OC₁₋₆alkyl, wherein eachalkyl is optionally fluorosubstituted.

In an embodiment, R³ is selected from Br, C₁ and F. In an embodiment, R³is F.

In an embodiment, R³ is selected from CH₃, CH₂CH₃, OCH₃, and OCH₂CH₃,wherein each alkyl is optionally fluorosubstituted. In an embodiment, R³is selected from CH₃, OCH₃, CHF₂, OCHF₂, CH₂F, OCH₂F, CF₃ and OCF₃. Inan embodiment, R³ is selected from OCH₃ and OCF₃.

In an embodiment, R³ is (CH₂)₀₋₂aryl optionally substituted with one ormore of halo, OH, NH₂, C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl, OC₁₋₁₆alkyl,OC₂₋₆alkenyl, or OC₂-alkynyl, wherein each alkyl, alkenyl, and alkynylare optionally fluorosubstituted. In an embodiment, R³ is (CH₂)₀₋₂aryloptionally substituted with one or more of halo, OH, NH₂, C₁₋₆alkyl, andOC₁₋₆alkyl, wherein each alkyl, alkenyl, and alkynyl are optionallyfluorosubstituted. In an embodiment, R³ is (CH₂)₀₋₂aryl.

In an embodiment, R³ is in the para position on the phenyl ring.

In an embodiment, R⁴ is H or CH₃.

In an embodiment, the plant is a canola, soybean, canary, sorghum,lentil, chickpea, Arabidopsis, faba bean, soybean, corn, rice, wheat,rye, barley, or fruit plant.

In an embodiment, the plant is a canola, lentil, chickpea, Arabidopsis,faba bean, soybean, corn, rice, wheat, rye, barley, or fruit plant.

In an embodiment, the plant is a lentil, soybean, canary, wheat, canola,rice, barley, or sorghum plant.

In an embodiment, the fruit plant is table or wine grapes.

In an embodiment, the fruit plant is a stone fruit plant. In anembodiment, the stone fruit plant is apricot, cherry, peach or plum.

In an embodiment, the fruit plant is strawberry, blueberry, raspberry,or blackberry.

In an embodiment, the fruit plant is pome fruit. In an embodiment, thepome fruit is apple, pear, or cherry.

In an embodiment, fruit plant is eggplant, pepper, or tomato.

In an embodiment, the fruit plant is cucurbit. In an embodiment, thecurcubit is cucumber, pumpkin, muskmelon, squash, or zucchini.

In an embodiment, the fruit plant is a tree nut plant. In an embodiment,the tree nut plant is walnut, chestnut, or hickory.

In an embodiment, the plant is leafy vegetable, or pasture and turfgrass.

In an embodiment, the plant is oat, flax, mustard, ornamental, or sugarcane.

In the context of reducing adverse affects of an ABA response, aneffective amount of the compound of Formula II or an enantiomer, saltand/or solvate thereof, is an amount that, for example, reduces theadverse affects compared to the negative response without administrationof the compound of Formula II, or an enantiomer, salt and/or solvatethereof.

In an embodiment, the effective amount of the compound of Formula II isabout 0.1 μM to about 600 μM, about 1 μM to about 500 μM, or about 5 μMto about 250 μM.

In an embodiment, the ABA response arises from an ABA producing plantpathogen infection.

In an embodiment, the compound of the application or salt and/or solvatethereof and/or compound of Formula (II) or enantiomer, salt and/orsolvate thereof, is administered to the plant in a composition that isdiluted prior to use. In an embodiment that composition is an aqueoussolution. In an embodiment, the composition further comprises otheringredients common to agricultural products, such as, but not limitedto, fertilizers, wetting agents, stickers/spreaders and surfactants.

In an embodiment, the compound of the application or salt and/or solvatethereof or compound of Formula (II) or enantiomer, salt and/or solvatethereof, is applied to plants at any suitable rate, the selection ofwhich can be made by a person skilled in the art. Factors to considerinclude, for example, the identity and/or the age of the plant, theconcentration of the composition of the application and/or a combinationthereof.

In an embodiment, the seed of the plant is contacted with thecomposition of the application.

It will also be appreciated that the effective amount of a compositionof the application used for the administration or use may increase ordecrease over the course of a particular regime. In some instances,chronic administration or use is required. For example, the compositionof the application is administered or used in an amount and for aduration sufficient to regulate plant growth.

IV. Methods of Preparing the Compounds of the Application

Compounds of the present application or compounds of Formula (II) orenantiomer, salt and/or solvate thereof, can be prepared by varioussynthetic processes. The choice of particular structural features and/orsubstituents may influence the selection of one process over another.The selection of a particular process to prepare a given compound ofFormula (I) or Formula (II) is within the purview of the person of skillin the art. Some starting materials for preparing compounds of thepresent application are available from commercial chemical sources.Other starting materials, for example as described below, are readilyprepared from available precursors using straightforward transformationsthat are well known in the art. In the Schemes below showing thepreparation of compounds of the application, all variables are asdefined in Formula (I), unless otherwise stated,

In an embodiment, the compounds of Formula (1) wherein L is —C≡C— areprepared as shown in Scheme 1. Therefore, an ABA derivative of Formula Ain which X is a suitable leaving group such as iodide is coupled with anappropriate alkynyl compound of Formula B in a solvent such astetrahydrofuran (THF) and in the presence of a catalyst such astetrakis(triphenylphosphine)palladium(0) and cocatalyst such as copperiodide and a base such as triethylamine. In an embodiment, the reactantsand solvent are combined at room temperature (rt) and then reacted at ahigher temperature such as at about 95° C. or at about 100° C. In anembodiment, the reaction is carried out under an inert atmosphere, suchas under argon.

In an embodiment, the compounds of Formula (I)I wherein L is —C═C— orcompounds of Formula (II) or enantiomer, salt and/or solvate thereof,are prepared as shown in Scheme 2. Therefore, an ABA derivative ofFormula A in which X is a suitable leaving group such as iodide iscoupled with a suitable aryl-boronic acid compound of Formula C in asolvent such as a 9:1 mixture of tetrahydrofuran (THF) and water (H₂O)and in the presence of a catalyst such astetrakis(triphenylphosphine)palladium(0) and a base such as potassiumcarbonate. In an embodiment, the reactants and solvent are combined atroom temperature (rt) and then reacted at a higher temperature such asat about 90° C. In an embodiment, the reaction is carried out under aninert atmosphere, such as under argon.

A person of skill in the art would appreciate that a stereoisomer of acompound of Formula (I) or Formula (II), can also be prepared as shownin Scheme 1 or Scheme II starting with a compound of Formula A with theappropriate stereospecificity to provide the desired stereoisomer of thecompound of Formula (I) or Formula (II).

The ABA derivative of formula A can be synthesized through knownmethods, for example, using the synthetic procedures found in Arai, S.et al. 1999.

The alkynyl derivatives of Formula B or salts and/or solvates thereof,useful in the present application are available from commercial sourcesor can be prepared using methods known in the art.

The aryl-boronic acid compound of Formula C or salts and/or solvatesthereof, useful in the present application are available from commercialsources or can be prepared using methods known in the art.

The ABA antagonist 1001 can be synthesized through known methods, forexample, using the synthetic procedures found in Rajagopalan et al.2016.

The ABA antagonist 1002 can be synthesized through known methods, forexample, using the synthetic procedures found in Takeuchi et al 2014.

The formation of a desired compound salt is achieved using standardtechniques. For example, the neutral compound is treated with an acid orbase in a suitable solvent and the formed salt is isolated byfiltration, extraction or any other suitable method.

The formation of solvates will vary depending on the compound and thesolvate. In general, solvates are formed by dissolving the compound inthe appropriate solvent and isolating the solvate by cooling or using anantisolvent. The solvate is typically dried or azeotroped under ambientconditions. The selection of suitable conditions to form a particularsolvate can be made by a person skilled in the art. Examples of suitablesolvents are ethanol, water and the like. When water is the solvent, themolecule is referred to as a “hydrate”. The formation of solvates of thecompounds of the application or compounds of Formula (II) will varydepending on the compound and the solvate. In general, solvates areformed by dissolving the compound in the appropriate solvent andisolating the solvate by cooling or using an antisolvent. The solvate istypically dried or azeotroped under ambient conditions. The selection ofsuitable conditions to form a particular solvate can be made by a personskilled in the art.

Throughout the processes described herein it is to be understood that,where appropriate, suitable protecting groups will be added to, andsubsequently removed from, the various reactants and intermediates in amanner that will be readily understood by one skilled in the art.Conventional procedures for using such protecting groups as well asexamples of suitable protecting groups are described, for example, in“Protective Groups in Organic Synthesis”, T. W. Green, P. G. M. Wuts,Wiley-Interscience, New York, (1999). It is also to be understood that atransformation of a group or substituent into another group orsubstituent by chemical manipulation can be conducted on anyintermediate or final product on the synthetic path toward the finalproduct, in which the possible type of transformation is limited only byinherent incompatibility of other functionalities carried by themolecule at that stage to the conditions or reagents employed in thetransformation. Such inherent incompatibilities, and ways to circumventthem by carrying out appropriate transformations and synthetic steps ina suitable order, will be readily understood to one skilled in the art.Examples of transformations are given herein, and it is to be understoodthat the described transformations are not limited only to the genericgroups or substituents for which the transformations are exemplified.References and descriptions of other suitable transformations are givenin “Comprehensive Organic Transformations—A Guide to Functional GroupPreparations” R. C. Larock, VHC Publishers, Inc. (1989). References anddescriptions of other suitable reactions are described in textbooks oforganic chemistry, for example, “Advanced Organic Chemistry”, March, 4thed. McGraw Hill (1992) or, “Organic Synthesis”, Smith, McGraw Hill,(1994). Techniques for purification of intermediates and final productsinclude, for example, straight and reversed phase chromatography oncolumn or rotating plate, recrystallisation, distillation andliquid-liquid or solid-liquid extraction, which will be readilyunderstood by one skilled in the art.

EXAMPLES

The following non-limiting examples are illustrative of the presentapplication.

Example 1: Methyl(2Z,4E)-5-((S)-1-Hydroxy-2,6,6-trimethyl-4-oxo-3-(phenylethynyl)cyclohex-2-en-1-yl)-3-methylpenta-2,4-dienoate(1018)

Under argon, 3′-iodo-(S)-ABA methyl ester (Arai et al. 1999) (193.5 mg,0.48 mmol), tetrakis(triphenylphosphine)palladium (0) (273.5 mg, 0.24mmol) and copper (1) iodide (46 mg, 0.24 mmol) were transferred into aRBF and sequentially were added THE (5.0 mL), triethylamine (5.0 mL) andethynylbenzene (0.080 mL, 0.73 mmol) at rt. The flask was placed in anoil bath at 100° C. After stirring for 2 hours, the reaction was allowedto come to ambient temperature and diluted with ethyl acetate. Theorganic phase was washed with 1.2 M HCl twice, water once, brine once,dried over Na₂SO₄ and concentrated. The crude was fractionated by FCC(10% of ethyl acetate in toluene) to give the title compound (74 mg,41%).

¹H NMR (600 MHz, CDCl₃) δ 7.90 (1H, d, J=16.0 Hz), 7.46-7.55 (2H, m),7.28-7.33 (3H, m), 6.16 (1H, d, J=16.0 Hz), 5.75 (1H, s), 3.70 (3H, s),2.56 (1H, d, J=17.0 Hz), 2.45 (1H, d, J=17.0 Hz), 2.22 (3H, s), 2.00(3H, d, J=1.0 Hz), 1.13 (3H, s), 1.03 (3H, s).

Example 2:(2Z,4E)-5-((S)-1-Hydroxy-2,6,6-trimethyl-4-oxo-3-(phenylethynyl)cyclohex-2-en-1-yl)-3-methylpenta-2,4-dienoicacid (1019)

Under argon, 3′-iodo-(S)-ABA (1.00 g, 2.56 mmol),tetrakis(triphenylphosphine)palladium (0) (890 mg, 0.770 mmol) andcopper (I) iodide (147 mg, 0.772 mmol) were transferred into a roundbottom flask and THE (25 mL), triethylamine (5 mL) and ethynylbenzene(0.42 mL, 3.8 mmol) at room temperature were added sequentially. Theflask was lowered into an oil bath set to 95° C. After stirring for 1hour, the reaction was allowed to come to ambient temperature anddiluted with ethyl acetate. The organic phase was washed with 1.2 M HCltwice, brine once, dried over Na₂SO₄ and concentrated. The crude wasfractionated by FCC (20% to 40% of acetone in hexanes with 0.1% ofacetic acid) to give the title compound (720 mg, 77%).

¹H NMR (500 MHz, CDCl₃) δ 7.88 (1H, d, J=16.0 Hz, HC-4), 7.50-7.54 (2H,m, HC-13′ x2), 7.29-7.34 (3H, m, HC-14′ x2, HC-15′), 6.18 (1H, d, J=16.0Hz, HC-5), 5.76 (1H, s, HC-2), 2.58 (1H, d, J=17.0 Hz, HC-5′), 2.46 (1H,d, J=17.0 Hz, HC-5′), 2.21 (3H, s, H₃C-7′), 2.04 (3H, d, J=1.0 Hz,H₃C-6), 1.14 (3H, s), 1.04 (3H, s).

¹³C NMR (125 MHz, CDCl₃) δ 194.0 (s, C-4′), 170.5 (s, C-1), 165.2 (s,C-2′), 151.7 (s, C-3), 136.3 (d, C-5), 132.0 (d, C-13′ x2), 128.9 (d,C-4), 128.7 (d, C-15′), 128.4 (d, C-14′ x2), 123.2 (s, C-12′), 122.6 (s,C-3′), 118.2 (d, C-2), 97.6 (s, C-11′), 83.0 (s, C-10′), 80.2 (s, C-1′),49.6 (t, C-5′), 41.1 (s, C-6′), 24.5 (q), 23.3 (q), 21.6 (q, C-6), 18.4(q, C-7′).

HRMS m/z calcd. for C₂₃H₂₄O₄+Na⁺ 387.1567, found 387.1586 (ESI).

Example 3:(2Z,4E)-5-((S)-1-Hydroxy-3-((4-methoxyphenyl)ethynyl)-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl)-3-methylpenta-2,4-dienoicacid (1021)

Under argon, 3′-iodo-(S)-ABA (108 mg, 0.277 mmol),tetrakis(triphenylphosphine)palladium (0) (160 mg, 0.138 mmol) andcopper (I) iodide (27 mg, 0.14 mmol) were transferred to a RBF andsequentially was added THE (2.7 mL), triethylamine (2.7 mL) and1-ethynyl-4-methoxybenzene (54 mg, 0.41 mmol) at room temperature. Thesuspension was placed in an oil bath at 100° C. After stirring for 2hours, the reaction was allowed to come to ambient temperature anddiluted with ethyl acetate. The organic phase was washed with 1.2 M HCltwice, brine once, dried over Na₂SO₄ and concentrated. The crude wasfractionated by FCC (20% to 40% of acetone in hexanes with 0.1% ofacetic acid) to give the title compound (67 mg, 61%).

¹H NMR (500 MHz, CDCl₃) δ 7.89 (1H, d, J=16.0 Hz, HC-4), 7.46 (2H, ap d,J=9.0 Hz, HC-13′ x2), 6.84 (2H, ap d, J=9.0 Hz, HC-14′ x2), 6.18 (1H, d,J=16.0 Hz, HC-5), 5.77 (1H, s, HC-2), 3.81 (3H, s, H₃CO), 2.57 (1H, d,J=17.0 Hz, HC-5′), 2.46 (1H, d, J=17.0 Hz, HC-5′), 2.20 (3H, s, H₃C-7′),2.04 (3H, d, J=1.0 Hz, H₃C-6), 1.13 (3H, s), 1.04 (3H, s).

¹³C NMR (125 MHz, CDCl₃) δ 194.1 (s, C-4′), 170.1 (s, C-1), 164.4 (s,C-2′), 160.0, (s, C-15′), 151.7 (s, C-3), 136.4 (d, C-5), 133.5 (d,C-13′ x2), 128.7 (d, C-4), 122.7 (s, C-3′), 118.1 (d, C-2), 115.3 (s,C-12′), 114.1 (d, C-14′ x2), 97.7 (s, C-11′), 81.8 (s, C-10′), 80.2 (s,C-1′), 55.5 (q, C-16′), 49.6 (t, C-5′), 41.1 (s, C-6′), 24.5 (q), 23.3(q), 21.6 (q, C-6), 18.3 (q, C-7′).

HRMS m/z calcd. for C₂₄H₂₆O₅+Na⁺ 417.1672, found 417.1686 (ESI).

Example 4:(2Z,4E)-5-((S)-3-((4-Fluorophenyl)ethynyl)-1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl)-3-methylpenta-2,4-dienoicacid (1022)

Under argon, 3′-iodo-(S)-ABA (97 mg, 0.25 mmol),tetrakis(triphenylphosphine)palladium (0) (144 mg, 0.124 mmol) andcopper (I) iodide (24 mg, 0.13 mmol) were transferred to a RBF andsequentially were added THE (2.5 mL), triethylamine (2.5 mL) and1-ethynyl-4-fluorobenzene (44 mg, 0.37 mmol) at rt. The suspension wasplaced in an oil bath at 95° C. After stirring for 1 hour, the reactionwas allowed to come to ambient temperature and diluted with ethylacetate. The organic phase was washed with 1.2 M HCl twice, brine once,dried over Na₂SO₄ and concentrated. The crude was fractionated by FCC(40% of diethyl ether in toluene with 0.1% of acetic acid) to give thetitle compound (46 mg, 48%).

¹H NMR (500 MHz, CDCl₃) δ 7.87 (1H, d, J=16.0 Hz, HC-4), 7.47-7.53 (2H,m, HC-13′ x2), 6.97-7.05 (2H, m, HC-14′ x2), 6.17 (1H, d, J=16.0 Hz,HC-5), 5.76 (1H, s, HC-2), 2.57 (1H, d, J=17.0 Hz, HC-5′), 2.45 (1H, d,J=17.0 Hz, HC-5′), 2.19 (3H, s, H₃C-7′), 2.04 (3H, d, J=1.0 Hz, H₃C-6),1.14 (3H, s), 1.04 (3H, s).

¹³C NMR (125 MHz, CDCl₃) δ 194.1 (s, C-4′), 170.3 (s, C-1), 165.3 (s,C-2′), 162.9 (s, C-15′, ¹J_(CF)=249.8 Hz), 151.7 (s, C-3), 136.3 (d,C-5), 133.9 (d, C-13′ x2, ³J_(CF)=8.4 Hz), 128.9 (d, C-4), 122.4 (s,C-3′), 119.3 (s, C-12′, ⁴J_(CF)=3.5 Hz), 118.2 (d, C-2), 115.8 (d, C-14′x2, ²J_(CF)=22.1 Hz), 97.5 (s, C-11′), 82.7 (s, C-10′), 80.2 (s, C-1′),49.6 (t, C-5′), 41.2 (s, C-6′), 24.5 (q), 23.3 (q), 21.6 (q, C-6), 18.4(q, C-7′).

HRMS m/z calcd. for C₂₃H₂₃FO₄+Na⁺ 405.1473, found 405.1456 (ESI).

Example 5:(2Z,4E)-5-((S)-1-Hydroxy-2,6,6-trimethyl-4-oxo-3-((4-(trifluoromethoxy)phenyl)ethynyl)cyclohex-2-en-1-yl)-3-methylpenta-2,4-dienoicacid (1023)

Under argon, 3′-iodo-(S)-ABA (100 mg, 0.256 mmol),tetrakis(triphenylphosphine)palladium (0) (149 mg, 0.129 mmol) andcopper (I) iodide (25 mg, 0.13 mmol) were transferred to a RBF andsequentially was added THE (2.6 mL), triethylamine (2.6 mL) and1-ethynyl-4-(trifluoromethoxy)benzene (0.07 mL, 0.5 mmol) at roomtemperature. The suspension was placed in an oil bath at 95° C. Afterstirring for 1 hour, the reaction was allowed to come to ambienttemperature and diluted with ethyl acetate. The organic phase was washedwith 1.2 M HCl twice, brine once, dried over Na₂SO₄ and concentrated.The crude was fractionated by FCC (40% of diethyl ether in toluene with0.1% of acetic acid) to give the title compound (71 mg, 61%).

¹H NMR (500 MHz, CDCl₃) δ 7.87 (1H, d, J=16.0 Hz, HC-4), 7.54 (2H, ap d,J=8.5 Hz, HC-13′ x2), 7.16 (2H, ap d, J=8.5 Hz, HC-14′ x2), 6.17 (1H, d,J=16.0 Hz, HC-5), 5.76 (1H, s, HC-2), 2.57 (1H, d, J=17.0 Hz, HC-5′),2.46 (1H, d, J=17.0 Hz, HC-5′), 2.19 (3H, s, H₃C-7′), 2.04 (3H, d, J=1.0Hz, H₃C-6), 1.14 (3H, s), 1.04 (3H, s).

¹³C NMR (125 MHz, CDCl₃) δ 194.0 (s, C-4′), 170.3 (s, C-1), 165.9 (s,C-2′), 151.7 (s, C-3), 149.3 (s, C-15′, ³J_(CF)=1.9 Hz), 136.3 (d, C-5),133.5 (d, C-13′ x2), 129.0 (d, C-4), 122.3 (s, C-3′), 121.9 (s, C-12′),120.9 (d, C-14′ x2, ⁴J_(CF)=1.1 Hz), 120.6 (s, C-16′, ¹J_(CF)=257.9 Hz),118.2 (d, C-2), 96.0 (s, C-11′), 83.8 (s, C-10′), 80.2 (s, C-1′), 49.5(t, C-5′), 41.2 (s, C-6′), 24.5 (q), 23.3 (q), 21.6 (q, C-6), 18.5 (q,C-7′).

HRMS m/z calcd. for C₂₄H₂₃F₃O₄+Na⁺ 471.1395, found 471.1409 (ESI).

Example 6:(2Z,4E)-5-((S)-1-Hydroxy-2,6,6-trimethyl-4-oxo-3-((4-phenoxyphenyl)ethynyl)cyclohex-2-en-1-yl)-3-methylpenta-2,4-dienoicacid (1024)

Under argon, 3′-iodo-(S)-ABA (100 mg, 0.256 mmol),tetrakis(triphenylphosphine)palladium (0) (148 mg, 0.128 mmol) andcopper (I) iodide (26 mg, 0.14 mmol) were transferred to a RBF andsequentially were added THE (2.6 mL), triethylamine (2.6 mL) and1-ethynyl-4-phenoxybenzene (0.07 mL, 0.4 mmol) at rt. The suspension wasplaced in an oil bath at 95° C. After stirring for 1 hour, the reactionwas allowed to come to ambient temperature and diluted with ethylacetate. The organic phase was washed with 1.2 M HCl twice, brine once,dried over Na₂SO₄ and concentrated. The crude was fractionated by FCC(30% of acetone in hexanes with 0.1% of acetic acid) to give the titlecompound (77 mg, 65%).

¹H NMR (500 MHz, CDCl₃) δ 7.88 (1H, bd, J=16.0 Hz, HC-4), 7.48 (2H, d,J=8.5 Hz, HC-13′ x2), 7.35 (2H, dd, J=7.5, 8.5 Hz, HC-18′ x2), 7.14 (1H,t, J=7.5 Hz, HC-19′), 7.02 (2H, d, J=8.5 Hz, HC-17′ x2), 6.92 (2H, d,J=8.5 Hz, HC-14′ x2), 6.17 (1H, d, J=16.0 Hz, HC-5), 5.78 (1H, bs,HC-2), 2.57 (1H, d, J=17.0 Hz, HC-5′), 2.46 (1H, d, J=17.0 Hz, HC-5′),2.20 (3H, s, H₃C-7′), 2.04 (3H, s, H₃C-6), 1.14 (3H, s), 1.04 (3H, s).

¹³C NMR (125 MHz, CDCl₃) δ 194.2 (s, C-4′), 170.1 (s, C-1), 165.0 (s,C-2′), 158.0 (s, C-15′), 156.5 (s, C-16′), 151.7 (s, C-3), 136.4 (d,C-5), 133.6 (d, C-13′ x2), 130.1 (d, C-18′ x2), 128.8 (d, C-4), 124.1,(d, C-19′), 122.6 (s, C-3′), 119.7 (d, C-17′ x2), 118.4 (d, C-14′ x2),118.2 (d, C-2), 117.6 (s, C-12′), 97.2 (s, C-11′), 82.4 (s, C-10′), 80.2(s, C-1′), 49.6 (t, C-5′), 41.1 (s, C-6′), 24.5 (q), 23.3 (q), 21.6 (q,C-6), 18.4 (q, C-7′).

HRMS m/z calcd. for C₂₉H₂₃O₅+Na⁺ 479.1829, found 479.1849 (ESI).

Example 7:(2Z,4E)-5-((S)-3-((4-Ethylphenyl)ethynyl)-1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl)-3-methylpenta-2,4-dienoicacid (1025)

Under argon, 3′-iodo-(S)-ABA (101 mg, 0.259 mmol),tetrakis(triphenylphosphine)palladium (0) (149 mg, 0.129 mmol) andcopper (I) iodide (25 mg, 0.13 mmol) were transferred to a RBF andsequentially were added THE (2.6 mL), triethylamine (2.6 mL) and1-ethyl-4-ethynylbenzene (0.06 mL, 0.4 mmol) at rt. The flask was placedin an oil bath at 95° C. After stirring for 1 hour, the reaction wasallowed to come to ambient temperature and diluted with ethyl acetate.The organic phase was washed with 1.2 M HCl twice, brine once, driedover Na₂SO₄ and concentrated. The crude was fractionated by FCC (30% ofdiethyl ether in toluene with 0.1% of acetic acid) to give the titlecompound (61 mg, 59%.

¹H NMR (500 MHz, CDCl₃) δ 7.87 (1H, d, J=16.0 Hz, HC-4), 7.43 (2H, d,J=8.0 Hz, HC-13′ x2), 7.14 (2H, d, J=8.0 Hz, HC-14′ x2), 6.17 (1H, d,J=16.0 Hz, HC-5), 5.77 (1H, s, HC-2), 2.64 (2H, q, J=7.5 Hz, H₂C-16′),2.57 (1H, d, J=17.0 Hz, HC-5′), 2.46 (1H, d, J=17.0 Hz, HC-5′), 2.19(3H, s, H₃C-7′), 2.04 (3H, d, J=1.0 Hz, H₃C-6), 1.22 (3H, t, J=7.5 Hz,H₃C-17′), 1.13 (3H, s), 1.03 (3H, s).

¹³C NMR (125 MHz, CDCl₃) δ 194.2 (s, C-4′), 170.3 (s, C-1), 165.0 (s,C-2′), 151.7 (s, C-3), 145.2 (s, C-15′), 136.4 (d, C-5), 132.0 (d, C-13′x2), 128.8 (d, C-4), 128.0 (d, C-14′ x2), 122.6 (s, C-3′), 120.3 (s,C-12′), 118.2 (d, C-2), 97.8 (s, C-11′), 82.3 (s, C-10′), 80.2 (s,C-1′), 49.6 (t, C-5′), 41.1 (s, C-6′), 29.0 (t, C-16′), 24.5 (q), 23.3(q), 21.6 (q, C-6), 18.3 (q, C-7′), 15.5 (q, C-17′).

HRMS m/z calcd. for C₂₅H₂₃O₄+Na⁺ 415.1885, found 415.1881 (ESI).

Example 8:(2Z,4E)-5-((S)-3-(3-ethyl-3-hydroxypent-1-yn-1-yl)-1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl)-3-methylpenta-2,4-dienoicacid (1059)

Under argon, 3′-iodo-(S)-ABA (105 mg, 0.27 mmol),tetrakis(triphenylphosphine)palladium (0) (94 mg, 0.081 mmol) and copper(I) iodide (16 mg, 0.084 mmol) were transferred to a RBF andsequentially were added THE (2.7 mL), triethylamine (0.54 mL) and3-ethyl-1-pentyn-3-ol (0.05 mL, 0.4 mmol) at rt. The flask was placed inan oil bath at 95° C. After stirring for 1 hour, the reaction wasallowed to come to ambient temperature and diluted with ethyl acetate.The organic phase was washed with 1.2 M HCl twice, brine once, driedover Na₂SO₄ and concentrated. The crude was fractionated by FCC (30% ofacetone in hexanes with 0.1% of acetic acid) to give the title compound(56 mg, 55%).

¹H NMR (500 MHz, CDCl₃) δ 7.77 (1H, d, J=16.0 Hz, HC-4), 6.13 (1H, d,J=16.0 Hz, HC-5), 5.77 (1H, bs, HC-2), 2.50 (1H, d, J=17.0 Hz, HC-5′),2.37 (1H, d, J=17.0 Hz, HC-5′), 2.13 (3H, s, H₃C-7′), 2.04 (3H, s,H₃C-6), 1.67-1.81 (4H, m, H₂C-13′ x2), 1.10 (3H, s), 1.08 (6H, dt,J=1.5, 7.5 Hz, H₃C-14′ x2), 1.03 (3H, s).

¹³C NMR (125 MHz, CDCl₃) δ 194.5 (s, C-4′), 170.5 (s, C-1), 165.3 (s,C-2′), 151.5 (s, C-3), 136.3 (d, C-5), 129.1 (d, C-4), 122.3 (s, C-3′),118.6 (d, C-2), 100.5 (s, C-11′), 80.4 (s, C-10′), 77.8 (s, C-1′), 72.8(s, C-12′), 49.5 (t, C-5′), 41.2 (s, C-6′), 34.50 (t, C-13′), 34.45 (t,C-13′), 24.4 (q), 23.3 (q), 21.6 (q, C-6), 18.6 (q, C-7′), 8.93 (q,C-14′), 8.91 (q, C-14′).

HRMS m/z calcd. for C₂₂H₃₀O₅+Na⁺ 397.1985, found 397.1973 (ESI).

Example 9:(2Z,4E)-5-((S)-1-hydroxy-3-((Z)-5-hydroxy-3-methylpent-3-en-1-yn-1-yl)-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl)-3-methylpenta-2,4-dienoicacid (1063)

Under argon, 3′-iodo-(S)-ABA (205 mg, 0.526 mmol),tetrakis(triphenylphosphine)palladium (0) (184 mg, 0.16 mmol) and copper(I) iodide 29.5 mg, 0.15 mmol) were weighted into a RBF and sequentiallyadded THE (5.4 mL), triethylamine (1.1 mL) and(Z)-3-methylpent-2-en-4-yn-1-ol (81.5 mg, 0.85 mmol) at rt. The flaskwas placed in an oil bath at 95° C. After stirring for 1 hour, thereaction was allowed to come to ambient temperature and diluted withethyl acetate. The organic phase was washed with 1.2 M HCl twice, brineonce, dried over Na₂SO₄ and concentrated. The crude was fractionated byFCC (40% of acetone in hexanes with 0.1% of acetic acid) to give thetitle compound (95.5 mg, 51%).

¹H NMR (500 MHz, CDCl₃) δ 7.76 (1H, d, J=16.0 Hz, HC-4), 6.13 (1H, d,J=16.0 Hz, HC-5), 5.99 (1H, dt, J=1.0, 6.5 Hz, HC-13′), 5.76 (1H, s,HC-2), 4.35 (2H, dd, J=6.5, 6.5 Hz, H₂C-14′), 2.52 (1H, d, J=17.0 Hz,HC-5′), 2.40 (1H, d, J=17.0 Hz, HC-5′), 2.15 (3H, s, H₃C-7′), 2.03 (3H,d, J=1.0 Hz, H₃C-6), 1.94 (3H, d, J=1.0 Hz, H₃C-15′), 1.10 (3H, s), 1.04(3H, s).

¹³C NMR (125 MHz, CDCl₃) δ 194.7 (s, C-4′), 169.7 (s, C-1), 165.3 (s,C-2′), 151.0 (s, C-3), 136.8 (d, C-13′), 136.1 (d, C-5), 129.1 (d, C-4),122.5 (s, C-3′), 121.7 (s, C-12′), 118.2 (d, C-2), 96.1 (s, C-11′), 87.8(s, C-10′), 80.3 (s, C-1′), 60.9 (t, C-14′), 49.5 (t, C-5′), 41.2 (s,C-6′), 24.4 (q), 23.3 (q), 23.0 (q, C-15′), 21.5 (q, C-6), 18.7 (q,C-7′).

HRMS m/z calcd. for C₂₁H₂₆O₅+Na⁺ 381.1672, found 381.1681 (ESI).

Example 10:(2Z,4E)-5-((S)-1-hydroxy-2,6,6-trimethyl-4-oxo-3-((E)-styryl)cyclohex-2-en-1-yl)-3-methylpenta-2,4-dienoicacid (1090)

Under argon, 3′-iodo-(S)-ABA (140 mg, 0.36 mmol),tetrakis(triphenylphosphine)palladium (0) (21 mg, 0.018 mmol),trans-2-phenylvinylboronic acid (108 mg, 0.72 mmol) and potassiumcarbonate (201 mg, 1.44 mmol) were transferred to a RBF and were added a9:1 mixture of THF, H₂O (7.2 mL). The flask was placed in an oil bath at90° C. After stirring for 24 hours, the reaction was allowed to come toambient temperature, cooled to 0° C. and quenched with 1N HCl. Themixture was diluted with ethyl acetate, separated the layers and theorganic phase was washed with brine once, dried over Na₂SO₄ andconcentrated. The crude was fractionated by FCC (40% of ethyl acetate inhexanes with 0.1% of acetic acid) to give the title compound (30 mg,23%).

¹H NMR (500 MHz, CDCl₃) δ 7.86 (1H, d, J=16.0 Hz, HC-4), 7.46 (2H, d,J=7.4 Hz, HC-13′), 7.32 (2H, t, J=7.4 Hz, HC-14′), 7.25 (1H, t, J=7.4Hz, HC-15′), 7.0 (1H, d, J=16.5 Hz, HC-11′), 6.84 (1H, d, J=16.5 Hz,HC-10′), 6.21 (1H, d, J=16.1 Hz, HC-5) 5.75 (1H, s, HC-2), 2.58 (1H, d,J=16.9 Hz, HC-5′), 2.42 (1H, d, J=16.9 Hz, HC-5′), 2.09 (1H, s, OH),2.05 (6H, s, H₃C-6, H₃C-7′), 1.14 (3H, s, H₃C-8′ or H₃C-9′), 1.04 (3H,s, H₃C-8′ or H₃C-9′).

¹³C NMR (125 MHz, CDCl₃) δ 197.1 (s, C-4′), 171.1 (s, C-1), 156.3 (s,C-2′), 152.0 (s, C-3), 137.7 (s, C-12′), 137.3 (d, C-5), 135.9 (d,C-11′), 133.4 (s, C-3′), 128.7 (d, C-14′), 128.6 (d, C-4), 128.0 (d,C-15′), 126.8 (d, C-13′), 121.6 (d, C-10′), 118.0 (d, C-2), 80.7 (s,C-1′), 50.2 (t, C-5′), 40.8 (s, C-6′), 24.7 (q, C-8′ or C-9′), 23.4 (q,C-8′ or C-9′), 21.7 (q, C-6), 16.7 (q, C-7′).

HRMS m/z calcd for C₂₃H₂₅O₄ (M-1) 365.1758, found 365.1744 (ESI).

Example 11:(2Z,4E)-5-((S)-1-hydroxy-3-((4-hydroxyphenyl)ethynyl)-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl)-3-methylpenta-2,4-dienoicacid (1091)

Under argon, 3′-iodo-(S)-ABA (157 mg, 0.40 mmol), 4-ethynylphenol²⁰ (94mg, 0.80 mmol), copper (I) iodide (39 mg, 0.20 mmol), triethylamine (0.8mL) and THE (4.0 mL) were transferred to a RBF and the mixture wasdegassed with argon for 10 minutes.Tetrakis(triphenylphosphine)palladium (0) (233 mg, 0.20 mmol) was addedto the reaction mixture and the flask was placed in an oil bath at 90°C. After stirring for 1.5 hours, the reaction was allowed to come toambient temperature, cooled to 0° C. and quenched with 1N HCl. Themixture was diluted with ethyl acetate, separated the layers and theorganic phase was washed with brine once, dried over Na₂SO₄ andconcentrated. The crude was fractionated by FCC (30% to 100% of ethylacetate in hexanes with 0.2% of acetic acid) to give a semi purecompound that was further purified through PTLC (15% of isopropanol inhexanes with 0.2% of acetic acid) to give the title compound (21 mg,14%).

1H NMR (500 MHz, CD₃OD) δ 7.81 (1H, d, J=16.1 Hz, HC-4), 7.35 (2H, d,J=8.7 Hz, HC-13′), 6.76 (2H, d, J=8.7 Hz, HC-14′), 6.27 (1H, d, J=16.1Hz, HC-5) 5.75 (1H, s, HC-2), 2.64 (1H, d, J=16.9 Hz, HC-5′), 2.34 (1H,d, J=16.9 Hz, HC-5′), 2.20 (3H, s, H₃C-7′), 2.05 (3H, d, J=1.0 Hz,H₃C-6), 1.07 (3H, s, H₃C-8′ or H₃C-9′), 1.04 (3H, s, H₃C-8′ or H₃C-9′).

¹³C NMR (125 MHz, CD₃OD) δ 197.2 (s, C-4′), 169.5 (s, C-1), 167.3 (s,C-2′), 159.3 (s, C-15′), 151.0 (s, C-3), 137.5 (s, C-5), 134.2 (d,C-13′), 129.8 (d, C-4), 123.4 (s, C-3′), 119.7 (d, C-2), 116.4 (d,C-14′), 115.1 (s, C-12′), 98.7 (s, C-11′), 81.8 (s, C-10′), 80.7 (s,C-1′), 50.4 (t, C-5′), 42.2 (s, C-6′), 24.7 (q, C-8′ or C-9′), 23.6 (q,C-8′ or C-9′), 21.3 (q, C-6), 18.8 (q, C-7′).

HRMS m/z calcd for C₂₃H₂₅O₅Na⁺ 403.1515, found 403.1530 (ESI).

Example 12:(2Z,4E)-5-((S)-3-(cyclohexylethynyl)-1-hydroxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl)-3-methylpenta-2,4-dienoicacid (1100)

Under argon, 3′-iodo-(S)-ABA (157 mg, 0.40 mmol), ethynylcyclohexane (87mg, 105 μL, 0.80 mmol), copper (I) iodide (39 mg, 0.20 mmol),triethylamine (0.8 mL) and THE (4.0 mL) were transferred to a RBF andthe mixture was degassed with argon for 10 minutes.Tetrakis(triphenylphosphine)palladium (0) (137 mg, 0.12 mmol) was addedto the reaction mixture and the flask was placed in an oil bath at 90°C. After stirring for 1.5 hours, the reaction was allowed to come toambient temperature, cooled to 0° C. and quenched with 1N HCl. Themixture was diluted with ethyl acetate, separated the layers and theorganic phase was washed with brine once, dried over Na₂SO₄ andconcentrated. The crude was fractionated by FCC (20% to 40% of ethylacetate in hexanes with 0.2% of acetic acid) to give the title compound(71 mg, 47%).

1H NMR (500 MHz, CDCl₃) δ 7.86 (1H, d, J=15.9 Hz, HC-4), 6.16 (1H, d,J=16.0 Hz, HC-5) 5.77 (1H, s, HC-2), 2.66-2.61 (1H, m, HC-12′), 2.51(1H, d, J=17.2 Hz, HC-5′), 2.41 (1H, d, J=17.2 Hz, HC-5′), 2.11 (3H, s,H₃C-7′), 2.04 (3H, d, J=1.1 Hz, H₃C-6), 1.89-1.83 (2H, m, HC-13′),1.76-1.69 (2H, m, HC-14′), 1.56-1.49 (3H, m, HC-13′, HC-15′), 1.36-1.31(3H, m, HC-14′, HC-15′), 1.1 (3H, s, H₃C-8′ or H₃C-9′), 1.0 (3H, s,H₃C-8′ or H₃C-9′).

¹³C NMR (125 MHz, CDCl₃) δ 194.7 (s, C-4′), 170.9 (s, C-1), 164.1 (s,C-2′), 151.8 (s, C-3), 136.6 (s, C-5), 128.5 (d, C-4), 122.7 (s, C-3′),118.1 (d, C-2), 103.2 (s, C-11′), 80.0 (s, C-1′), 74.0 (s, C-10′), 49.5(t, C-5′), 41.0 (s, C-6′), 32.7 (t, C-13′), 30.0 (d, C-12′), 26.1 (t,C-15′), 25.0 (d, C-14′), 24.5 (q, C-8′ or C-9′), 23.3 (q, C-8′ or C-9′),21.6 (q, C-6), 18.1 (q, C-7′).

HRMS m/z calcd for C₂₃H₃₀O₄Na⁺ 393.2036, found 393.2055 (ESI).

Example 13:(2Z,4E)-5-((S)-3-hydroxy-2,4,4-trimethyl-6-oxo-3,4,5,6-tetrahydro-[1,1′-biphenyl]-3-yl)-3-methylpenta-2,4-dienoicacid(1080).¹⁷

Under argon, 3′-iodo-(S)-ABA (45 mg, 0.11 mmol),tetrakis(triphenylphosphine)palladium (0) (13 mg, 0.011 mmol),phenylboronic acid (17 mg, 0.14 mmol) and potassium carbonate (77 mg,0.55 mmol) were transferred to a RBF and were added a 9:1 mixture ofTHF, H₂O (2.0 mL). The flask was placed in an oil bath at 90° C. Afterstirring for 21 hours, the reaction was allowed to come to ambienttemperature, cooled to 0° C. and quenched with 1N HCl. The mixture wasdiluted with ethyl acetate, separated the layers and the organic phasewas washed with brine once, dried over Na₂SO₄ and concentrated. Thecrude was fractionated by PTLC (10% of methanol in dichloromethane) togive the title compound (16 mg, 41%).

¹H NMR (500 MHz, CDCl₃) δ 7.86 (1H, d, J=16.2 Hz, HC-4), 7.36 (2H, t,J=7.2 Hz, HC-12′), 7.29 (1H, t, J=7.4 Hz, HC-13′), 7.07 (2H, d, J=7.0Hz, HC-11′), 6.26 (1H, d, J=16.2 Hz, HC-5) 5.79 (1H, s, HC-2), 2.60 (1H,d, J=17.0 Hz, HC-5′), 2.43 (1H, d, J=17.0 Hz, HC-5′), 2.08 (3H, s,H₃C-6), 1.70 (3H, s, H₃C-7′), 1.21 (3H, s, H₃C-8′ or H₃C-9′), 1.08 (3H,s, H₃C-8′ or H₃C-9′).

¹³C NMR (125 MHz, CDCl₃) δ 196.7 (s, C-4′), 171.1 (s, C-1), 157.2 (s,C-2′), 151.5 (s, C-3), 138.8 (s, C-3′), 137.5 (d, C-5), 135.8 (s,C-10′), 129.9 (d, C-11′), 128.6 (d, C-4), 128.4 (d, C-12′), 127.6 (d,C-13′), 118.5 (d, C-2), 80.4 (s, C-1′), 49.8 (t, C-5′), 41.3 (s, C-6′),24.6 (q, C-8′ or C-9′), 23.3 (q, C-8′ or C-9′), 21.6 (q, C-6), 17.4 (q,C-7′).

HRMS m/z calcd for C₂₁H₂₃O₄ (M-1) 339.1601, found 339.1591 (ESI).

Example 14: Studying the Effect of Exemplary Compounds of theApplication and Exemplary Compounds of Formula (II) on Lentil (CDCMaxim) Germination Methodology

40 seeds were counted for each 100×15 mm petri dishes. Each petri dishcontained two filter papers and 10 mL of test solutions. Then, they werewrapped with aluminium foil to cut off light. Wrapped plates were kepton lab bench at room temperature. Germinated seeds were counted everydayuntil one treatment reaches 100% germination (two days). Only lightexposure was during plate counting.

The following dosages were used when studying the effect of differentexemplary compounds on lentil:

1 μM Compound 10 μM Compound 1 μM Compound+10 μM ABA 10 μM Compound+10μM ABA

All seeds from this experiment have been rinsed first with tap water andthen with dH₂O, frozen in liquid nitrogen and stored at −80° C. freezer.

Results

The effect of exemplary compound 1019 used alone or in combination withABA on percent lentil seed germination at dosage of 10:100 μM on day 1and 2 compared to ABA alone is shown in FIGS. 1A/B and FIG. 2. Theeffect of exemplary compounds of the application (1019, 1021-1025) andcomparative compounds (ABA, 1001) on percent lentil seed germination onday 1 and day 2 after having been treated with 1 μM Compound alone, 10μM Compound alone, 1 μM Compound+10 μM ABA or 10 μM Compound+10 μM ABAis shown in FIG. 3A and FIG. 3B, respectively. Seed germination was mosthighly promoted by exemplary compound 1025 at 1 uM. 10 uM ABA alonecompletely inhibited seed germination (FIG. 3A). Exemplary compounds ofthe application at 10 uM promoted germination in the presence of 10 uMABA (FIG. 3A). Seed germination was not affected by exemplary compoundsof the application alone at 1 or 10 uM (FIG. 3B). Exemplary compound ofthe application overcame ABA-inhibition at 1:1 ratio of exemplarycompound to ABA (FIG. 3B). FIG. 4 shows images of the lentil seeds aftersimilar treatment.

As shown in FIG. 5, lentil seed germination in the presence of 10 μM ABAwas promoted by 10 μM exemplary compound 1019 and 10 μM exemplarycompound 1019 plus 10 μM ABA and by 100 μM exemplary compound 1090 and100 μM exemplary compound 1090 plus 10 μM ABA and both compoundtreatments were comparable or higher in germination percentage thancontrol. Lentil seed germination was found to be weakly promoted by 100μM exemplary compound of Formula (II) 1080 in the presence of 10 μM ABAcompared to control. In FIGS. 6 A-C, data is presented comparing theeffects of exemplary compound 1019 with exemplary compounds 1091 and1100. The exemplary compounds 1091 and 1100 at 100 μM had no effect onseed germination compared to control. In FIG. 6B 100 μM solutions ofexemplary compounds 1019, 1091 and 1100 overcame the effect of added 10μM ABA. In FIG. 6C, the results of comparison of 10 μM ABA plus 10 μM ofeither exemplary compounds 1019, 1091 or 1100 are displayed. All threewere found to be effective antagonists, with the strongest antagonist inthis assay being exemplary compound 1019, followed by exemplary compound1091 and exemplary compound 1100. Exemplary compound 1059 and 1063 werefound to have no agonist activity and weak antagonist activity whentested at 10 uM versus 10 uM ABA (data not shown).

Example 15: Studying the Effect of Exemplary Compounds of theApplication on Soybean (AAC Edward; 2018) Germination Methodology

For each treatment 6 replicates of 10 seeds were plated into petridishes lined with two filter papers and 10 mL of test solution. Thecovered dishes were stored at room temperature in the dark. Germinatedseeds were counted over 24 hours. The following dosages were used whenstudying the effect of exemplary compounds of the application on soybeangermination: control 1% DMSO. 10 μM ABA, 10 μM exemplary compound 1019,100 μm exemplary compound 1019, 10 μM exemplary compound 1019 plus 10 μMABA and 100 uM exemplary compound 1019 plus 10 μM ABA.

Results

The results are very similar to those found in lentil seed germinationstudies. Both were carried out with the exemplary compound 1019 and theexemplary compound alone at 10 or 100 μM concentration did not affectseed germination. However in the presence of 10 μM ABA both 10 and 100μM exemplary compound 1019 overcame the inhibition caused by ABA.

Example 16: Studying the Effect of Exemplary Compounds of theApplication on Canary Seed Germination (CDC Bastia; 2018; CANYT1 Rep1;Kernen) Methodology

For each treatment 6 replicates of 30 seeds were plated into petridishes lined with two filter papers and 10 mL of test solution. Thecovered dishes were stored at room temperature in the dark. Germinatedseeds were counted over 24 hours. The following dosages were used whenstudying the effect of exemplary compounds on soybean germination:control 1% DMSO. 10 μM ABA, 10 μM exemplary compound 1019, 100 μMexemplary compound 1019, 10 μM exemplary compound 1019 plus 10 μM ABAand 100 μM exemplary compound 1019 plus 10 μM ABA.

Results

Neither concentration of exemplary compound 1019 affected germination ofcanary seed. 100 μM of exemplary compound 1019 overcame inhibition by 10μM ABA on day 4 while 10 μM exemplary compound 1019 did not.

Example 17: Studying the Effects of Exemplary Compounds of theApplication on Hard Red Spring Wheat Seedling Growth Methodology

For each treatment 3 replicates of 10 seeds were plated into petridishes lined with two filter papers and 10 mL of test solution. Thecovered dishes were stored at room temperature in the dark. At 72 hours,germinated seeds were scored for root length and shoot length. Thefollowing dosages were used when studying the effect of the exemplaryABA analogues of the application on wheat shoot and root growth: control1% DMSO. 10 μM ABA, 10 μM 1019, 100 μM exemplary compound 1019, 10 μMexemplary compound 1019 plus 10 μM ABA (10:1) and 100 μM exemplarycompound 1019 plus 10 μM ABA (1:1).

Results

Root growth was not affected by 100 μM exemplary compound 1019 alone,but was by 10 μM ABA. 100 μM exemplary compound 1019 plus 10 μM ABA and10 μM exemplary compound 1019 and 10 μM (FIG. 9 A) ABA both restoredroot growth to close to control length. Shoot growth was not inhibitedby 100 μM exemplary compound 1019 and was inhibited by 10 μM ABA. Growthof shoots was restored with exemplary compound 1019, but to a lesserextent than root growth (FIG. 9 B).

Example 18: Studying the Effect of Exemplary Compounds of theApplication on Canola Seed (Nutrien PV200) Germination Methodology

For each treatment 6 replicates of 40 seeds were plated into petridishes lined with two filter papers and 10 mL of test solution. Thecovered dishes were stored at room temperature in the dark. Germinatedseeds were counted every 2 days for 8 days. The following dosages wereused when studying the effect of exemplary compounds on canolagermination: control 1% DMSO. 10 μM ABA, 100 μM 1019, and 100 μM 1019plus 10 μM ABA.

Results

As shown in FIG. 10, 10 μM ABA inhibited seed germination throughout the8 day study. The exemplary compound 1019 at 100 μM did not significantlyaffect germination compared to the control treatment. With the 100 μMexemplary compound 1019 plus 10 μM ABA treatment, the extent ofgermination was restored to near control levels.

Example 19: Studying the Effect of Exemplary Compound 1019 on Rice,Barely, Wheat and Sorghum Seed Germination/Radical ElongationMethodology

Seeds were surface sterilized by incubation in 10% bleach for 20 minwith shaking, then rinsed four times with sterile water. Four ml of testsolutions were pipetted into petri dishes (100×15 mm) that contain asingle filter paper. Fifteen seeds were added to each dish. For rice,barely, and wheat, the experiment involved five treatments (5 μM ABA; 5μM ABA+10 μM 1019; 10 μM 1019; water control; water+EtOH+NaOH control),with three replications per treatment. For sorghum, treatments were 10μM ABA; 10 μM ABA+20 μM 1019; 20 μM 1019; water control; water+EtOH+NaOHcontrol. Dishes were sealed with Parafilm, and incubated in the dark atroom temperature. Radical length was measured daily post emergence usingImageJ software; shown are 3 days post treatment for barley, wheat andsorghum and 4.5 days post treatment for rice.

Results

Using the concentrations and conditions described here, ABA did notinhibit seed germination, but did inhibit radical elongation. ABAinhibition of radical elongation was observed in assays with rice,barley and wheat at 5 μM ABA (FIGS. 11A-C), and for sorghum at 10 μM ABA(FIG. 11D). The higher rate of ABA application was used for sorghumbecause inconsistent results were observed at the lower rates. Additionof 10 μM exemplary compound 1019 blocked the effects of exogenouslyadded ABA on rice, barley and wheat radical elongation (FIGS. 11A-C).The effects of exemplary compound 1019 on sorghum are not clear becausethe exemplary compound itself significantly reduces radical elongation(FIG. 11D).

Example 20: Studying the Effect of Exemplary Compound 1019 on SeedGermination in Wild and RIL Populations of Lentil Genotypes; and in FabaBean Methodology

Fifty four lentil genotypes were selected for the experiment based onthe existing data on the number of days it takes them to emerge and daysto flowering. The seeds of each genotype were scarified before sowingand subjected to 3 treatments. VWR 415 9 cm filter papers were placedinside VWR 100 mm plastic petri dishes. Each petri dish was labeled onboth the top and the bottom. Ten seed from each line was place in alabelled petri dish. Each lentil or faba bean genotype was replicated 3times and subjected to 3 treatments (total number of experimental petridishes=531). Thus:

-   -   1. ABA exemplary compound solution [10 μM exemplary ABA analog        compound 1019 in 1% DMSO, 99% H₂O (LL10.1014.1) NaSaH        (SL-1-16-1-53)]    -   2. No exemplary ABA analogue solution (1% DMSO, 99% H₂O)    -   3. Distilled water—control

Seven milliliters of either exemplary ABA analogue solution, solutionwith no exemplary ABA analogue or distill water (control) was added intothe corresponding labelled petri dishes containing the 10 scarifiedlentil seeds. For faba bean, 10 ml because of their large seed size. Thepetri dishes were placed in a dark cupboard. Two digital temperature andhumidity loggers (Tinytag) were placed inside the cupboards to monitorenvironmental conditions.

Germination was considered for a seed when a tiny radicle at least 5 mmor greater had emerged from the seed. The number of seeds thatgerminated was counted and recorded at 48 and 96 hours; and at 7 days.Some of the genotypes of interest were photographed (AF-S Micro NIKKOR60 mm 1:2.8G camera) for comparison purpose. However, an excel sheetshowing all results is available. At 48 hours, a total of 22 genotypesand their replicates were selected from the petri dishes treated withexemplary compound and distilled water were transplanted into pots (forfaba bean) and trays (for lentils) in order to assess the length of timethey took to flower while the rest of the petri dishes were kept tillthe end of the experiment that lasted a week.

The average temperature in the cupboards was 22.5° C. (±0.3) while therelative humidity ranged from 52.4 to 80.7 percent for the duration ofthe experiment. Studies carried out by Linda Gorim and Devini De Silva,University of Saskatchewan

Results

Of the 54 lentil genotypes screened for response to exemplary compound1019 in improving germination rate over 4 days, 18 responded positively.Of the responsive genotypes four were L. orientalis, and six were L.nigricans and the remaining belonged either to the other wild lentilgenotypes or RIL lines. For example, the genotype L. nigricans IG-72551seeds had 100% germination at 2 days when exemplary compound 1019 wasutilized while the water and solvent control had no seeds germinated at4 days. Also, L. orientalis IG72770 treated with exemplary compound 1019had 40% germination at day 2, 75% at day 3 and 100% at day 4 while bothcontrols had zero germination in the same time period.

Overall, for all genotypes that responded to exemplary compound 1019,the treatment with the exemplary compound eliminated the variablegermination rates that were observed between replicates in the controlsand during emergence especially in wild germplasm. Therefore, exemplarycompound 1019 does not only speed up germination rates but also resultedin germination uniformity. This significant reduction in germinationtime can have a significant impact on the number of crossing block thatare carried per year in the lentil breeding program, i.e. many morecrossed carried out per year. However, there was no significant effectof the exemplary compound 1019 on germination rates in faba bean nor didit significantly affect the days to flowering in either legume.

Example 21: Studying the Effect of Exemplary Compound 1019 on LentilGermination, Emergence & Time to Flowering Methodology Abbreviations

DSTG=Days from seeding to germination

DSTE=Days from seeding to Emergence

DSTF=Days from seeding to flowering

DSTH=Days from seeding to harvesting of first seed (F7 was not includedbecause the purpose of this generation was to harvest as many seeds aspossible)

GA₃=gibberellic acid

DMSO=solvent required for dissolving 1019-ABA

F7 Experiment

Objective: Testing the effect of soaking seeds of the F7 generation infour solutions listed below.

Treatments: water, DMSO, 1019-ABA, and 1019-ABA for 1 day followed by100 μM GA₃

Plant material: Seeds derived from a cross between L. culinaris varRedberry and L. culinaris ssp. orientalis IG72595

Experimental set up: 207 RIL-lines in total; 4 seeds (repetitions) perline; 4 treatments

Data collection: Days from seeding to germination (DSTG), days fromseeding to emergence (DSTE), and Days from seeding to first flower werecounted. Days from seeding to first harvest was not determined becausewe needed as many seeds as possible in this generation.

Results

Days to germination (DSTG), emergence (DSTE), time to flowering (DSTF)and first harvest (DSTH) were determined during the development of arecombinant inbred line (RIL) developed from a cross between L.culinaris var Redberry and L. culinaris ssp. orientalis IG72595. The aimof the project was to find and incorporate Aphanomyces root rotresistance into the cultivated lentil, and the L. orientalis accessionwas identified with improved resistance. During the development of thisRIL line speed breeding techniques were applied i.e. warmertemperatures, longer day length, higher light intensity, restricted potvolume etc. In generation F5, the exemplary compound became availableand was tested on germination and emergence. It was noted that not onlydid seeds germinate and emerge faster but that days to flowering wasalso reduced. This resulted in a shorter generation length i.e. daysfrom seeding to harvest of first seed. The F7 generation was set up as aproper experiment with four treatments i.e. 1019, water, DMSO (solventneeded for dissolving exemplary compound 1019), and exemplary compound1019 for one day followed by 100 μM GA₃(FIG. 12).

TABLE 1 Number of lines seeded per generation (F2-F7), number of seedsgerminated & emerged, as well as number of days from seeding togermination, emergence, flowering & harvest. Generation Seeded Germ.Emerged DSTG DSTE DSTF DSTH

F2 282 282 282 N.D. N.D. 37.58 58.07

F3 282 282 282 N.D. N.D. 39.20 69.16

F4 261 257 248 2.70 6.33 36.51 54.84

F5 231 230 225 2.18 4.93 28.22 45.41 1019 F6 226 226 226 1.12 4.03 26.1444.02 1019 F7 819 816 791 1.49 4.31 24.94 N.D 1019

indicates data missing or illegible when filed

Table 2 shows that 99% of seeds germinated in the exemplary compound1019 treatment compared to only 96% when seeds were germinated in water.Table 2 below shows that 99% of seeds germinated within 2 days in theexemplary compound 1019 treatment. In contrast, seeds soaked in watergerminated much slower over a longer time period i.e. only 20%germinated within 2 days. Surprisingly, DMSO alone also speeded upgermination but was slower by one day and the germination rate was loweras well.

TABLE 2 Overview of seeding and germination data Treatment Line # Seed #Lost % Lost Seeds Germ. % Germ. Water 207 822 16 2.0 806 770 96.4 DMSO207 817 12 1.5 805 779 96.8 1019&GA 207 821 7 0.9 814 791 97.2 1019-ABA207 819 3 0.4 816 807 98.9 Total 2460 35 4.3 2425 2340 Average 615.08.75 1.1 606.3 585.0 96.5

Four days after seeding 81% of the exemplary compound 1019-treated seedshad already emerged compared to 11% in the DMSO and 7% in the watertreatments (FIG. 12B). Therefore, seeds treated with exemplary compound1019 not only germinated faster and over a shorter time period but alsoemerged faster and at a rate of 100% compared to 89% and 84%,respectively. It should be noted that DMSO had little effect onemergence.

Next, we analyzed the number of days from seeding to flowering for eachtreatment. Exemplary compound 1019 treated seeds flowered 4 days earlieron average than plants from the water treatment (Table 3).

TABLE 3 Treatment DSTF Water 29.4 DMSO 27.6 GA&1019 25.6 1019 24.9

In conclusion, exemplary compound 1019 significantly reduced the numberof days from seeing to germination (root growth) compared to thecontrols (water and 1% DMSO in water). Seeds needed 1.5 days togerminate with exemplary compound 1019 and 4.5 days with water.Exemplary compound 1019 did not improve emergence (shoot growth)compared to the controls. It took 5.3 days seedlings emerged fasterafter using DMSO (5.1 days) or 1019+GA₃ (5.1 days) but differences weresmall. Using exemplary compound 1019 for germination resulted in fasterflowering compared to the controls. It took 1019 plants 25 days todevelop the first flower. It took 28 (1% DMSO in water) and 29 (water)days for plants to flower. Exemplary compound 1019 treatment resulted inplants flowering 4 days earlier. Using exemplary compound 1019 treatmentresulted in seeds germinating (ca. 99%) within 2 days. Compared to seedsimbibed in water in which case germination was slow and took place over9 days. The synchronizing of germination improves the processsignificantly.

Example 22: Studying the Effect of Exemplary Compound of the Applicationon ABA-Inducible Gene Expression in Arabidopsis Methodology

Transgenic MKKK18GUS Arabidopsis plants harbor an α-glucuronidase (GUS)reporter gene fused to an ABA-inducible promoter of the MKKK18 gene(Okamoto et al. 2013). Six-day-old MKKK18GUS plants were treated withABA1019 alone or both ABA1019 and ABA for 6 hours. Plants were thenstained with 5-bromo-4-chloro-3-indolyl-beta-D-glucuronic acidcyclohexyl ammonium salt (X-Glc) for 14 hours, and destained with 70%ethanol.

Results

As shown in FIG. 13 exemplary compound 1019 at 2.5 μM has a weak agonistactivity when applied alone, while it showed a potent antagonist effectin a dose dependent manner when co-applied with 2.5 M ABA. When appliedat 1:1 ratio with ABA, a reduction in the GUS staining was observed whencompared to application of ABA alone. Increasing the ratio of exemplarycompound 1019 to ABA to 10:1 resulted in abolition of the ABA GUS stainshowing clear antagonism of ABA by exemplary compound 1019.

Example 23: Studying the Effect of Exemplary Compound 1019 on the PlantPathogen Botrytis Cinerea Methodology

Analogs of ABA that antagonize ABA have the potential to overcomenegative effects of ABA in plant pathogen interactions. To test thishypothesis, we conducted a pathogenicity test on leaves of Arabidopsisthaliana plants against a virulent Botrytis cinerea strain ofArabidopsis (Mathys et al., 2012)²¹ Col-0 plants were sprayed withexemplary compound 1019 (100 μM) or mock control. After 24 h, leaveswere detached and inoculated with mycelium blocks of Botrytis cinereagrown on PDA medium plates. Results

Pathogenicity assays revealed that symptom development was slower onleaves treated with the exemplary compound 1019 than that of mockcontrol. At 24 hours post inoculation, disease lesions surrounding theinoculated sites were observed in control leaves, but smaller lesionsappeared on the leaves treated with the exemplary compound (FIG. 14).These preliminary results indicate that the treatment with exemplarycompound 1019 partially inhibits the disease development caused byABA-producing fungal pathogen, B. cinerea. The delay of diseasedevelopment could be caused by either a direct inhibitory impact on B.cinerea development or activation of host defenses.

FULL CITATIONS FOR DOCUMENTS REFERRED TO IN THE APPLICATION

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1. A compound of Formula (I) or an enantiomer, salt, and/or solvatethereof:

wherein L is —C═C— or —C═C—; R¹ is C₁₋₁₀alkyl, C₂₋₁₀alkenyl,C₂₋₁₀alkynyl, (CH₂)₀₋₂C₃₋₁₀cycloalkyl, (CH₂)₀₋₂aryl,(CH₂)₀₋₂heterocycloalkyl, or (CH₂)₀₋₂heteroaryl, each being optionallysubstituted with one or more of halo, CN, OH, NH₂, C₁₋₁₀alkyl,C₂₋₁₀alkenyl, C₂₋₁₀alkynyl, NH(C₁₋₆alkyl), N(C₁₋₆alkyl)(C₁₋₆ alkyl),OC₁₋₆alkyl, OC₂₋₆alkenyl, OC₂₋₆alkynyl, (CH₂)₀₋₂C₃₋₁₀cycloalkyl,(CH₂)₀₋₂aryl, (CH₂)₀₋₂heterocycloalkyl, (CH₂)₀₋₂heteroaryl,O(CH₂)₀₋₂C₃₋₁₀cycloalkyl, O(CH₂)₀₋₂aryl, O(CH₂)₀₋₂heterocycloalkyl, orO(CH₂)₀₋₂heteroaryl, the latter 16 groups being optionally substitutedwith one or more of halo, OH, NH₂, C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl,OC₁₋₆alkyl, OC₂₋₆alkenyl, or OC₂₋₆alkynyl; and R² is H, C₁₋₁₀alkyl,C₂₋₁₀alkenyl, C₂₋₁₀alkynyl, cycloalkyl, aryl, heterocycloalkyl orheteroaryl, the latter 7 groups being optionally substituted with one ormore of halo, OH, NH₂, C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl, OC₁₋₁₆alkyl,OC₂₋₆alkenyl, or OC₂₋₆alkynyl, wherein each alkyl, alkenyl, and alkynylare optionally fluorosubstituted.
 2. The compound of claim 1, wherein R¹is (CH₂)₀₋₂aryl optionally substituted with one or more of halo, CN, OH,NH₂, C₁₋₁₀alkyl, C₂₋₁₀alkenyl, C₂₋₁₀alkynyl, NH(C₁₋₆alkyl),N(C₁₋₆alkyl)(C₁₋₆alkyl), OC₁₋₆alkyl, OC₂₋₆alkenyl, OC₂₋₆alkynyl,(CH₂)₀₋₂C₃₋₁₀cycloalkyl, (CH₂)₀₋₂aryl, (CH₂)₀₋₂heterocycloalkyl,(CH₂)₀₋₂heteroaryl, O(CH₂)₀₋₂C₃₋₁₀cycloalkyl, O(CH₂)₀₋₂aryl,O(CH₂)₀₋₂heterocycloalkyl or O(CH₂)₀₋₂heteroaryl, the latter 16 groupsbeing optionally substituted with one or more of halo, OH, NH₂,C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl, OC₁₋₁₆alkyl, OC₂₋₆alkenyl, orOC₂₋₆alkynyl, wherein each alkyl, alkenyl, and alkynyl are optionallyfluorosubstituted.
 3. (canceled)
 4. The compound of claim 1, wherein R¹is aryl optionally substituted with one or more of OH, halo, C₁₋₁₀alkyl,OC₁₋₆alkyl, or O(CH₂)₀₋₂aryl, wherein each alkyl, alkenyl, and alkynylare optionally fluorosubstituted. 5.-13. (canceled)
 14. The compound ofclaim 1, wherein R¹ is C₁₋₁₀alkyl optionally substituted with one ormore of halo, CN, OH, NH₂, C₁₋₁₀alkyl, C₂₋₁₀alkenyl, C₂₋₁₀alkynyl,NH(C₁₋₆alkyl), N(C₁₋₆alkyl)(C₁₋₆alkyl), OC₁₋₆alkyl, OC₂₋₆alkenyl,OC₂₋₆alkynyl, (CH₂)₀₋₂C₃₋₁₀cycloalkyl, (CH₂)₀₋₂aryl,(CH₂)₀₋₂heterocycloalkyl, (CH₂)₀₋₂heteroaryl, O(CH₂)₀₋₂C₃₋₁₀cycloalkyl,O(CH₂)₀₋₂aryl, O(CH₂)₀₋₂heterocycloalkyl, or O(CH₂)₀₋₂heteroaryl, thelatter 16 groups being optionally substituted with one or more of halo,OH, NH₂, C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl, OC₁₋₁₆ alkyl,OC₂₋₆alkenyl, or OC₂₋₆alkynyl, wherein each alkyl, alkenyl, and alkynylare optionally fluorosubstituted.
 15. The compound of claim 14, whereinR¹ is C₁₋₁₀alkyl optionally substituted with one or more of halo, CN,OH, NH₂, C₁₋₁₀alkyl, C₂₋₁₀alkenyl, or C₂₋₁₀alkynyl, wherein each alkyl,alkenyl, and alkynyl are optionally fluorosubstituted.
 16. (canceled)17. The compound of claim 1, wherein R¹ is C₂₋₁₀alkenyl optionallysubstituted with one or more of halo, CN, OH, NH₂, C₁₋₁₀alkyl,C₂₋₁₀alkenyl, or C₂₋₁₀alkynyl, wherein each alkyl, alkenyl, and alkynylare optionally fluorosubstituted.
 18. (canceled)
 19. The compound ofclaim 1, wherein R¹ is (CH₂)₀₋₂C₃₋₁₀cycloalkyl optionally substitutedwith one or more of halo, CN, OH, NH₂, C₁₋₁₀alkyl, C₂₋₁₀alkenyl,C₂₋₁₀alkynyl, NH(C₁₋₆alkyl), N(C₁₋₆alkyl)(C₁₋₆alkyl), OC₁₋₆alkyl,OC₂₋₆alkenyl, OC₂₋₆alkynyl, (CH₂)₀₋₂C₃₋₁₀cycloalkyl, (CH₂)₀₋₂aryl,(CH₂)₀₋₂heterocycloalkyl, (CH₂)₀₋₂heteroaryl, O(CH₂)₀₋₂C₃₋₁₀cycloalkyl,O(CH₂)₀₋₂aryl, O(CH₂)₀₋₂heterocycloalkyl, or O(CH₂)₀₋₂heteroaryl, thelatter 16 groups being optionally substituted with one or more of halo,OH, NH₂, C₁₋₆alkyl, C₂₋₆alkenyl, C₂₋₆alkynyl, OC₁₋₁₆alkyl, OC₂₋₆alkenyl,or OC₂₋₆alkynyl, wherein each alkyl, alkenyl, and alkynyl are optionallyfluorosubstituted.
 20. The compound of claim 19, wherein R¹ isC₃₋₁₀cycloalkyl optionally substituted with one or more of halo, CN, OH,NH₂, C₁₋₁₀alkyl, C₂₋₁₀alkenyl, or C₂₋₁₀alkynyl, wherein each alkyl,alkenyl, and alkynyl are optionally fluorosubstituted.
 21. The compoundof claim 1, wherein R² is H or C₁₋₁₀alkyl.
 22. (canceled)
 23. Thecompound of claim 1, wherein L is —C═C—.
 24. The compound of claim 1,wherein L is —C≡C—.
 25. The compound of Formula (I) or a salt, and/orsolvate thereof of claim 1, wherein the compound has the followingstereochemistry:


26. The compound of Formula (I) of claim 1 selected from the compoundslisted below: Compound I.D Structures 1018

1019

1021

1022

1023

1024

1025

1059

1063

1090

1091

1100

or a salt, and/or solvate thereof.


27. (canceled)
 28. A method for reducing adverse effects of an ABAresponse in a plant in need thereof comprising administering aneffective amount of one or more compounds of claim 1 or salt and/orsolvate thereof to the plant.
 29. (canceled)
 30. The method of claim 28,wherein the adverse effects of an ABA response include delayed orinhibited seed germination and/or plant dessication, over-ripening offruit, slow bud breaking and/or slow plant growth.
 31. The method ofclaim 28, wherein the adverse effects of an ABA response occur understress conditions. 32.-35. (canceled)
 36. A method for reducing adverseeffects of an ABA response in a plant in need thereof comprisingadministering an effective amount of one or more compounds of theFormula (II) or an enantiomer, salt, and/or solvate thereof, to theplant,

wherein: n is 0, 1, 2 or 3; R³ is selected from OH, halo, C₁₋₁₀alkyl,OC₁₋₆alkyl, and O(CH₂)₀₋₂aryl, the latter 3 groups being optionallysubstituted with one or more of halo, OH, NH₂, C₁₋₆alkyl, C₂₋₆alkenyl,C₂₋₆alkynyl, OC₁₋₁₆alkyl, OC₂₋₆alkenyl, or OC₂₋₆alkynyl; and R⁴ isselected from H or C₁₋₁₀alkyl, wherein each alkyl, alkenyl, and alkynylis optionally fluorosubstituted.
 37. The method of claim 36, wherein theeffective amount of the compound is about 0.1 μM to about 600 μM, about1 μM to about 500 μM, or about 5 μM to about 250 μM
 38. The method ofclaim 28, wherein the plant is canola, lentil, chickpea, Arabidopsis,faba bean, soybean, corn, rice, wheat, rye, barley, or fruit plant.39-53. (canceled)
 54. The method of claim 28, wherein one or morecompounds of claim 1 or salt and/or solvate thereof or the compound ofFormula II as defined in claim 36 or salt and/or solvate thereof isadministered in combination with other known agents useful forregulating plant development.
 55. (canceled)
 56. (canceled)